Annotations¶
VIP annotates variant effects and genotype data for samples using a rich set of tools. Annotions can be used to classify variants using classification trees and displayed in reports.
Overview¶
The table contains annotations available in most output files. Depending on the workflow and the configuration used additional annotations might be available, check the output file headers for the complete overview. Similarly, some annotations listed below might be missing from your output file depending on the sample sheet content and configuration.
Filter¶
| annotation | value | source | description |
|---|---|---|---|
| FILTER | base_qual | GATK | alt median base quality |
| FILTER | clustered_events | GATK | Clustered events observed in the tumor |
| FILTER | contimation | GATK | contamination |
| FILTER | duplicate | GATK | evidence for alt allele is overrepresented by apparent duplicates |
| FILTER | FAIL | GATK | Fail the site if all alleles fail but for different reasons. |
| FILTER | fragment | GATK | abs(ref - alt) median fragment length |
| FILTER | germline | GATK | Evidence indicates this site is germline, not somatic |
| FILTER | haplotype | GATK | Variant near filtered variant on same haplotype. |
| FILTER | low_allele_frac | GATK | Allele fraction is below specified threshold |
| FILTER | map_qual | GATK | ref - alt median mapping quality |
| FILTER | MONOALLELIC | GLnexus | Site represents one ALT allele in a region with multiple variants that could not be unified into non-overlapping multi-allelic sites |
| FILTER | multiallelic | GATK | Site filtered because too many alt alleles pass tumor LOD |
| FILTER | n_ratio | GATK | Ratio of N to alt exceeds specified ratio |
| FILTER | normal_artifact | GATK | artifact_in_normal |
| FILTER | orientation | GATK | orientation bias detected by the orientation bias mixture model |
| FILTER | panel_of_normals | GATK | Blacklisted site in panel of normals |
| FILTER | PASS | Straglr | All filters passed |
| FILTER | position | GATK | median distance of alt variants from end of reads |
| FILTER | possible_numt | GATK | Allele depth is below expected coverage of NuMT in autosome |
| FILTER | q5 | cuteSV | Quality below 5 |
| FILTER | slippage | GATK | Site filtered due to contraction of short tandem repeat region |
| FILTER | strand_bias | GATK | Evidence for alt allele comes from one read direction only |
| FILTER | strict_strand | GATK | Evidence for alt allele is not represented in both directions |
| FILTER | UNRESOLVED | Spectre | An insertion that is longer than the read and thus we cannot predict the full size |
| FILTER | weak_evidence | GATK | Mutation does not meet likelihood threshold |
Format¶
| annotation | type | source | description |
|---|---|---|---|
| FORMAT/AD | integer | GATK | Allelic depths for the ref and alt alleles in the order listed |
| FORMAT/AF | float | GATK | Allele fractions of alternate alleles in the tumor |
| FORMAT/CD | float list | Spectre | Coverage read depth |
| FORMAT/DP | integer | Approximate read depth (reads with MQ=255 or with bad mates are filtered) | |
| FORMAT/DR | integer | cuteSV | # High-quality reference reads |
| FORMAT/DV | integer | cuteSV | # High-quality variant reads |
| FORMAT/F1R2 | integer | GATK | Count of reads in F1R2 pair orientation supporting each allele |
| FORMAT/F2R1 | integer | GATK | Count of reads in F2R1 pair orientation supporting each allele |
| FORMAT/FAD | integer | GATK | Count of fragments supporting each allele. |
| FORMAT/GQ | integer | cuteSV, Spectre, GATK | Genotype Quality |
| FORMAT/GT | string | cuteSV, Spectre, straglr-tsv2vcf, GATK | Genotype |
| FORMAT/HO | float list | Spectre | Homozygosity proportion |
| FORMAT/ID | string | Spectre | Population ID of supporting CNV calls |
| FORMAT/LC | integer | straglr-tsv2vcf | Locus coverage |
| FORMAT/PGT | string | GATK | Physical phasing haplotype information, describing how the alternate alleles are phased in relation to one another; will always be heterozygous and is not intended to describe called alleles |
| FORMAT/PL | integer list | cuteSV | # Phred-scaled genotype likelihoods rounded to the closest integer |
| FORMAT/PS | integer | Whatshap | Phase set identifier |
| FORMAT/RNC | character list | Reason for No Call in GT: . = n/a, M = Missing data, P = Partial data, I = gVCF input site is non-called, D = insufficient Depth of coverage, - = unrepresentable overlapping deletion, L = Lost/unrepresentable allele (other than deletion), U = multiple Unphased variants present, O = multiple Overlapping variants present, 1 = site is Monoallelic, no assertion about presence of REF or ALT allele | |
| FORMAT/RU_CALL | string | straglr-tsv2vcf | Most frequent actual repeat motif |
| FORMAT/RU_CI | string | straglr-tsv2vcf | 95% confidence interval per allele. 'NA' if less than 2 reads were present. |
| FORMAT/RU_MATCH | integer | straglr-tsv2vcf | RU call matches catalog (allowing shift/IUPAC, 1= match, 0 = mismatch |
| FORMAT/RU_NR | string | straglr-tsv2vcf | Number of repeat units per allele. |
| FORMAT/RU_SEEN | string | straglr-tsv2vcf | All RUs encountered with read counts |
| FORMAT/RU_SPAN | integer | straglr-tsv2vcf | Number of spanning reads per allele. |
| FORMAT/SB | integer | GATK | Per-sample component statistics which comprise the Fisher's Exact Test to detect strand bias. |
| FORMAT/VI | string list | vip-inheritance-matcher | An enumeration of possible inheritance modes (Possible values: AR, AR_C, AD, AD_IP, XLR, XLD) |
| FORMAT/VIAB | float | annotate process | VIP calculated allele balance |
| FORMAT/VIC | string | vip-inheritance-matcher | Possible Compound hetrozygote variants |
| FORMAT/VID | integer | vip-inheritance-matcher | De novo variant |
| FORMAT/VIG | string list | vip-inheritance-matcher | Genes with an inheritance match |
| FORMAT/VIM | integer | vip-inheritance-matcher | Inheritance Match: Genotypes, affected statuses and known gene inheritance patterns match |
| FORMAT/VIPC_S | string list | vip-decision-tree | VIP decision tree classification for sample |
| FORMAT/VIPP_S | string list | vip-decision-tree | VIP decision tree path for sample |
INFO¶
| annotation | type | source | description |
|---|---|---|---|
| INFO/AC | integer list | Allele count in genotypes | |
| INFO/AF | float list | cuteSV | Allele Frequency |
| INFO/AN | integer | Total number of alleles in called genotypes | |
| INFO/AQ | integer list | Allele Quality score reflecting evidence for each alternate allele (Phred scale) | |
| INFO/AS_FilterStatus | string | GATK | Filter status for each allele, as assessed by ApplyVQSR. Note that the VCF filter field will reflect the most lenient/sensitive status across all alleles. |
| INFO/AS_SB_TABLE | string | GATK | Allele-specific forward/reverse read counts for strand bias tests. Includes the reference and alleles separated by |. |
| INFO/AS_UNIQ_ALT_READ_COUNT | integer | GATK | Number of reads with unique start and mate end positions for each alt at a variant site |
| INFO/CHR2 | string | cuteSV | Chromosome for END coordinate in case of a translocation |
| INFO/CILEN | integer list | cuteSV | Confidence interval around inserted/deleted material between breakends |
| INFO/CIPOS | integer list | cuteSV | Confidence interval around POS for imprecise variants |
| INFO/CN | integer | Spectre | Estimated copy number status |
| INFO/CONTQ | float | GATK | Phred-scaled qualities that alt allele are not due to contamination |
| INFO/Disease | string | Stranger | Associated disorder |
| INFO/DisplayRU | string | Stranger | Display repeat unit familiar to clinician |
| INFO/DP | integer | GATK | Approximate read depth; some reads may have been filtered |
| INFO/ECNT | integer | GATK | Number of potential somatic events in the assembly region |
| INFO/ECNTH | integer | GATK | Number of somatic events in best supporting haplotype for each alt allele |
| INFO/END | integer | cuteSV, Spectre, straglr-tsv2vcf | End position of the structural variant |
| INFO/GERMQ | integer | GATK | Phred-scaled quality that alt alleles are not germline variants |
| INFO/HGNCId | integer | Stranger | HGNC gene id for associated disease gene |
| INFO/IMPRECISE | boolean | cuteSV | Imprecise structural variant |
| INFO/InheritanceMode | string | Stranger | Main mode of inheritance for disorder |
| INFO/MBQ | integere | GATK | median base quality by allele |
| INFO/MFRL | integer | GATK | median fragment length by allele |
| INFO/MMQ | integer | GATK | median mapping quality by allele |
| INFO/MPOS | integer | GATK | median distance from end of read |
| INFO/NALOD | float | GATK | Log 10 odds of artifact in normal with same allele fraction as tumor |
| INFO/NCount | integer | GATK | Count of N bases in the pileup |
| INFO/NLOD | float | GATK | Normal log 10 likelihood ratio of diploid het or hom alt genotypes |
| INFO/OCM | integer | GATK | Number of alt reads whose original alignment doesn't match the current contig. |
| INFO/OLD_REC | string | Original variant. Format: CHR|POS|REF|ALT|USED_ALT_IDX | |
| INFO/PON | flag | GATK | site found in panel of normals |
| INFO/POPAF | float | GATK | negative log 10 population allele frequencies of alt alleles |
| INFO/PRECISE | boolean | cuteSV | Precise structural variant |
| INFO/RankScore | string | Stranger | RankScore for variant in this family as family(str):score(int) |
| INFO/RE | integer | cuteSV | Number of read support this record |
| INFO/REPID | string | straglr-tsv2vcf | Locus identifier. |
| INFO/ROQ | float | GATK | Phred-scaled qualities that alt allele are not due to read orientation artifact |
| INFO/RPA | integer | GATK | Number of times tandem repeat unit is repeated, for each allele (including reference) |
| INFO/RU | string | GATK | Tandem repeat unit (bases) |
| INFO/RU_CAT | string | straglr-tsv2vcf | Catalog repeat motif |
| INFO/SEQQ | integer | GATK | Phred-scaled quality that alt alleles are not sequencing errors |
| INFO/Source | string | Stranger | Source collection for variant definition |
| INFO/SourceDisplay | string | Stranger | Source for variant definition, display |
| INFO/SourceId | string | Stranger | Source id for variant definition |
| INFO/STR | flag | GATK | Variant is a short tandem repeat |
| INFO/STR_NORMAL_MAX | integer | Stranger | Max number of repeats allowed to call as normal |
| INFO/STR_PATHOLOGIC_MIN | integer | Stranger | Min number of repeats required to call as pathologic |
| INFO/STR_STATUS | string list | Stranger | Repeat expansion status. Alternatives in [normal, pre_mutation, full_mutation] |
| INFO/STRAND | string list | cuteSV | Strand orientation of the adjacency in BEDPE format (DEL:+-, DUP:-+, INV:++/--) |
| INFO/STRANDQ | integer | GATK | Phred-scaled quality of strand bias artifact |
| INFO/STRQ | integer | GATK | Phred-scaled quality that alt alleles in STRs are not polymerase slippage errors |
| INFO/SVLEN | integer | cuteSV, Spectre | Length of the SV |
| INFO/SVSUPPORT | string | Spectre | Indicator if a SV support was found in a provided SNFJ file |
| INFO/SVTYPE | string | cuteSV, Spectre, straglr-tsv2vcf | Type of copy number variant |
| INFO/SweGenMean | float | Stranger | Average number of repeat unit copies in population |
| INFO/SweGenStd | float | Stranger | Standard deviation of number of repeat unit copies in population |
| INFO/TLOD | float | GATK | Log 10 likelihood ratio score of variant existing versus not existing |
| INFO/VIPC_S | string list | VIP decision tree classification (samples) |
INFO/CSQ¶
| annotation | type | source | description |
|---|---|---|---|
| INFO/CSQ/Allele | string | VEP | The variant allele used to calculate the consequence |
| INFO/CSQ/ALLELE_NUM | integer | VEP | Allele nr within the VCF file. |
| INFO/CSQ/ALPHSCORE | float | VEP plugin | AlphScore pathogenicity score for missense variants (see here) |
| INFO/CSQ/Amino_acids | string | VEP | Reference and variant amino acids |
| INFO/CSQ/apogee_Score | float | VEP plugin | APOGEE-2 pathogenicity score for mtDNA variants (used for protein coding genes) |
| INFO/CSQ/ASV_ACMG_class | string | VEP plugin | AnnotSv 'ACMG_class' output |
| INFO/CSQ/ASV_AnnotSV_ranking_criteria | string | VEP plugin | AnnotSv 'AnnotSV_ranking_criteria' output |
| INFO/CSQ/ASV_AnnotSV_ranking_score | string | VEP plugin | AnnotSv 'AnnotSV_ranking_score' output |
| INFO/CSQ/BIOTYPE | string | VEP | Biotype of transcript or regulatory feature |
| INFO/CSQ/CAPICE_CL | categorical | VEP plugin | CAPICE classification (see here). Categories: B, LB, VUS, LP, P |
| INFO/CSQ/CAPICE_SC | float | VEP plugin | CAPICE score |
| INFO/CSQ/cDNA_position | string | VEP | Position within the cDNA |
| INFO/CSQ/CDS_position | string | VEP | Position within the coding sequence |
| INFO/CSQ/CHECK_REF | string | VEP | Reports variants where the input reference does not match the expected reference |
| INFO/CSQ/CLIN_SIG | string list | VEP | ClinVar classification(s) (do not use, see here) |
| INFO/CSQ/clinVar_CLNID | integer list | VEP plugin | ClinVar variation identifier |
| INFO/CSQ/clinVar_CLNREVSTAT | categorical list | VEP plugin | ClinVar review status for the Variation ID. Categories: practice_guideline, reviewed_by_expert_panel, criteria_provided, _multiple_submitters, _no_conflicts, _single_submitter, _conflicting_interpretations, no_assertion_criteria_provided, no_assertion_provided |
| INFO/CSQ/clinVar_CLNSIG | string | VEP plugin | Clinical significance for this single variant; multiple values are separated by a vertical bar. Categories: Benign, Likely_benign, Uncertain_significance, Likely_pathogenic, Pathogenic, Conflicting_classifications_of_pathogenicity, Other |
| INFO/CSQ/clinVar_CLNSIGINCL | string | VEP plugin | Clinical significance for a haplotype or genotype that includes this variant. Reported as pairs of VariationID:clinical significance; multiple values are separated by a vertical bar. Categories: Benign, Likely_benign, Uncertain_significance, Likely_pathogenic, Pathogenic, Conflicting_interpretations_of_pathogenicity |
| INFO/CSQ/Codons | string | VEP | Reference and variant codon sequence |
| INFO/CSQ/Consequence | string list | VEP | Effect(s) described as Sequence Ontology term(s) |
| INFO/CSQ/DISTANCE | string | VEP | Shortest distance from variant to transcript |
| INFO/CSQ/existing_InFrame_oORFs | string | VEP plugin | The number of existing inFrame overlapping ORFs (inFrame oORF) at the 5 prime UTR |
| INFO/CSQ/existing_OutOfFrame_oORFs | string | VEP plugin | The number of existing out-of-frame overlapping ORFs (OutOfFrame oORF) at the 5 prime UTR |
| INFO/CSQ/existing_uORFs | string | VEP plugin | The number of existing uORFs with a stop codon within the 5 prime UTR |
| INFO/CSQ/Existing_variation | string list | VEP | Identifier(s) of co-located known variants |
| INFO/CSQ/EXON | string | VEP | The exon number (out of total number) |
| INFO/CSQ/Feature | string | VEP | RefSeq ID of feature |
| INFO/CSQ/Feature_type | categorical | VEP | VEP feature type. Categories: Transcript, RegulatoryFeature, MotifFeature |
| INFO/CSQ/FATHMM_MKL_NC | float | VEP plugin | The FATHMM-MKL score for Non-Coding Single Nucleotide Variants (SNVs) |
| INFO/CSQ/five_prime_UTR_variant_annotation | string | VEP plugin | Output the annotation of a given 5 prime UTR variant |
| INFO/CSQ/five_prime_UTR_variant_consequence | string | VEP plugin | Output the variant consequences of a given 5 prime UTR variant: uAUG_gained, uAUG_lost, uSTOP_lost or uFrameshift |
| INFO/CSQ/FLAGS | string list | VEP | Transcript quality flags (cds_start_NF: CDS 5' incomplete, cds_end_NF: CDS 3' incomplete) |
| INFO/CSQ/GADO_PD | categorical | VEP plugin | GADO prediction for the relation between the HPO terms of the proband(s) and the gene, HC: high confidence, LC: low confidence. Categories: LC, HC |
| INFO/CSQ/GADO_SC | float | VEP plugin | The combined prioritization GADO Z-score over the HPO of the proband(s) terms for this case |
| INFO/CSQ/Gene | string | VEP | NCBI Gene ID of affected gene |
| INFO/CSQ/gnomAD_COV | float | VEP plugin | gnomAD coverage (percent of individuals in gnomAD source) |
| INFO/CSQ/gnomAD_AF | float | VEP plugin | gnomAD allele frequency |
| INFO/CSQ/gnomAD_FAF95 | float | VEP plugin | gnomAD filter allele frequency (95% confidence) |
| INFO/CSQ/gnomAD_FAF99 | float | VEP plugin | gnomAD filter allele frequency (99% confidence) |
| INFO/CSQ/gnomAD_HN | integer | VEP plugin | gnomAD number of homozygotes |
| INFO/CSQ/gnomAD_QC | string list | VEP plugin | gnomAD quality control filters that failed |
| INFO/CSQ/gnomAD_SRC | categorical | VEP plugin | gnomAD source (E=exomes, G=genomes, T=total) |
| INFO/CSQ/Grantham | string | VEP plugin | Grantham Matrix score - Grantham, R. Amino Acid Difference Formula to Help Explain Protein Evolution, Science 1974 Sep 6;185(4154):862-4 |
| INFO/CSQ/HGNC_ID | integer | VEP | HGNC gene identifier |
| INFO/CSQ/HGVS_OFFSET | string | VEP | Indicates by how many bases the HGVS notations for this variant have been shifted |
| INFO/CSQ/HGVSc | string | VEP | HGVS nomenclature: coding DNA reference sequence |
| INFO/CSQ/HGVSp | string | VEP | HGVS nomenclature: protein reference sequence |
| INFO/CSQ/HIGH_INF_POS | string | VEP | A flag indicating if the variant falls in a high information position of a transcription factor binding profile (TFBP) |
| INFO/CSQ/hmtvar_DiseaseScore | float | VEP plugin | HmtVar disease score for mtDNA variants (used of tRNA genes) |
| INFO/CSQ/HPO | string list | VEP plugin | Human phenotype ontology term that match |
| INFO/CSQ/IMPACT | categorical | VEP | Impact as predicted by VEP. Categories: LOW, MODERATE, HIGH, MODIFIER |
| INFO/CSQ/IncompletePenetrance | string | VEP plugin | Boolean indicating if the gene is known for incomplete penetrance (1:true) |
| INFO/CSQ/InheritanceModesGene | string list | VEP plugin | List of inheritance modes for the gene |
| INFO/CSQ/INTRON | string | VEP | The intron number (out of total number) |
| INFO/CSQ/mitoTip_Score | float | VEP plugin | MitoTIP pathogenicity score for mtDNA variants (used for tRNA genes) |
| INFO/CSQ/mitoTip_Quartile | string | VEP plugin | MitoTIP pathogenicity score quartile |
| INFO/CSQ/MOTIF_NAME | string | VEP | The source and identifier of a transcription factor binding profile aligned at this position |
| INFO/CSQ/MOTIF_POS | string | VEP | The relative position of the variation in the aligned TFBP |
| INFO/CSQ/MOTIF_SCORE_CHANGE | string | VEP | The difference in motif score of the reference and variant sequences for the TFBP |
| INFO/CSQ/ncER | float | VEP plugin | The non-coding essential regulation (ncER) score indicates if a region is likely to be essential in terms of regulation. |
| INFO/CSQ/PHENO | integer list | VEP | Indicates if existing variant is associated with a phenotype, disease or trait; multiple values correspond to multiple values in the Existing_variation field |
| INFO/CSQ/phyloP | string | VEP custom | Conservation p-values, see here |
| INFO/CSQ/PICK | integer | VEP | Boolean indicating if this is the VEP picked transcript |
| INFO/CSQ/PolyPhen | float | VEP | PolyPhen score |
| INFO/CSQ/Protein_position | string | VEP | Position within the protein |
| INFO/CSQ/PUBMED | integer list | VEP | PubMed citations |
| INFO/CSQ/REFSEQ_MATCH | string | VEP | Flag indicating whether and how the RefSeq model differs from the underlying genome |
| INFO/CSQ/REFSEQ_OFFSET | string | VEP | ? |
| INFO/CSQ/ReMM | float | VEP plugin | The Regulatory Mendelian Mutation (ReMM) score was created for relevance prediction of non-coding variations in the human genome in terms of Mendelian diseases. |
| INFO/CSQ/SIFT | float | VEP | SIFT score |
| INFO/CSQ/SOMATIC | integer list | VEP | Somatic status of existing variant(s); multiple values correspond to multiple values in the Existing_variation field |
| INFO/CSQ/SOURCE | string | VEP | ? |
| INFO/CSQ/SpliceAI_pred_DP_AG | float | VEP plugin | SpliceAI predicted effect on splicing. Delta position for acceptor gain |
| INFO/CSQ/SpliceAI_pred_DP_AL | float | VEP plugin | SpliceAI predicted effect on splicing. Delta position for acceptor loss |
| INFO/CSQ/SpliceAI_pred_DP_DG | float | VEP plugin | SpliceAI predicted effect on splicing. Delta position for donor gain |
| INFO/CSQ/SpliceAI_pred_DP_DL | float | VEP plugin | SpliceAI predicted effect on splicing. Delta position for donor loss |
| INFO/CSQ/SpliceAI_pred_DS_AG | float | VEP plugin | SpliceAI predicted effect on splicing. Delta score for acceptor gain |
| INFO/CSQ/SpliceAI_pred_DS_AL | float | VEP plugin | SpliceAI predicted effect on splicing. Delta score for acceptor loss |
| INFO/CSQ/SpliceAI_pred_DS_DG | float | VEP plugin | SpliceAI predicted effect on splicing. Delta score for donor gain |
| INFO/CSQ/SpliceAI_pred_DS_DL | float | VEP plugin | SpliceAI predicted effect on splicing. Delta score for donor loss |
| INFO/CSQ/SpliceAI_pred_SYMBOL | string | VEP plugin | SpliceAI gene symbol |
| INFO/CSQ/STRAND | string | VEP | The DNA strand (1 or -1) on which the transcript/feature lies |
| INFO/CSQ/SYMBOL | string | VEP | Gene symbol |
| INFO/CSQ/SYMBOL_SOURCE | string | VEP | The source of the gene symbol |
| INFO/CSQ/TRANSCRIPTION_FACTORS | string | VEP | ? |
| INFO/CSQ/VIPC | string | vip-decision-tree | VIP decision tree classification for variant effect |
| INFO/CSQ/VIPP | string list | vip-decision-tree | VIP decision tree path for variant effect |
| INFO/CSQ/VKGL | string | VEP plugin | ? |
| INFO/CSQ/VKGL_CL | string | VEP plugin | VKGL consensus variant classification |
Details¶
VIP uses the Ensemble Effect Predictor to annotate all variants with their
consequences. We use VEP with the refseq option for the transcripts, and with the flags for sift and polyphen
annotations enabled.
Plugins¶
Below we describe the other sources which we annotate using the VEP plugin framework.
CAPICE¶
CAPICE is a computational method for predicting the pathogenicity of SNVs and InDels. It is a gradient boosting tree model trained using a variety of genomic annotations used by CADD score and trained on the clinical significance. CAPICE performs consistently across diverse independent synthetic, and real clinical data sets. It ourperforms the current best method in pathogenicity estimation for variants of different molecular consequences and allele frequency.
We run the CAPICE application in the VIP pipeline and use a VEP plugin to annotate the VEP output with the scores from the CAPICE output file.
VKGL¶
The datashare workgroup of VKGL has set up a central database to enable mutual sharing of variant classifications through a partly automatic process. An additional goal is the public sharing of these data. The currently publicly available part of the database consists of DNA variant classifications established based on (former) diagnostic questions.
We add the classifications from an export of the database and use a VEP plugin to annotate the VEP output with the classifications from the this file.
SpliceAI¶
SpliceAI is an open-source deep learning splicing prediction algorithm that has demonstrated in the past few years its high ability to predict splicing defects caused by DNA variations.
We add the scores from the available precomputed scores of SpliceAI and use a copy of the available VEP plugin to annotate the VEP output with the classifications from the this file.
AnnotSV¶
AnnotSV is a program for annotating and ranking structural variations from genomes of several organisms.
We run the AnnotSV application in the VIP pipeline and use a VEP plugin to annotate the VEP output with the scores from the AnnotSV output file.
HPO¶
A file based on the HPO phenotype_to_genes.txt is used to annotate VEP consequences with the inheritance modes associated with the gene of this consequence.
Inheritance¶
A file based on the CGD database is used to annotate VEP consequences with the inheritance modes associated with the gene of this consequence.
Grantham¶
The Grantham score attempts to predict the distance between two amino acids, in an evolutionary sense. A lower Grantham score reflects less evolutionary distance. A higher Grantham score reflects a greater evolutionary distance.
We use a copy of the VEP plugin by Duarte Molha to annotate the VEP output with Grantham scores.
GADO¶
GADO can be used to prioritize genes based on the HPO terms of a patient..
We run the GADO commandline application in the VIP pipeline and use a VEP plugin to annotate the VEP output with the scores from the GADO output file.
AlphScore¶
AlphScore is a method to predict the pathogenicity of missense variants using features derived from AlphaFold2.
We add the available precomputed scores of AlphScore using a custom VEP plugin.
ncER¶
The non-coding essential regulation (ncER) score indicates if a region is likely to be essential in terms of regulation. The ncER file VIP uses is the version provided by GREEN-VARAN (https://github.com/edg1983/GREEN-VARAN) on Zenodo: https://zenodo.org/records/5636163 If overlapping regions are encountered (which can occur in liftovered resources) the highest score is annotated.
ReMM¶
The Regulatory Mendelian Mutation (ReMM) score was created for relevance prediction of non-coding variations (SNVs and small InDels) in the human genome (hg19) in terms of Mendelian diseases. The VEP plugin is build on top of the GREEN-DB dataset (GRCh38) for ReMM scores: https://zenodo.org/records/3955933 If overlapping regions are encountered (which can occur in liftovered resources) the highest score is annotated.
FATHMM-MKL¶
FATHMM-MKL predicts the Functional Consequences of Coding and Non-Coding Single Nucleotide Variants (SNVs) This plugin annotates non-coding scores only, and is build on top of the GREEN-DB dataset (GRCh38) for FATHMM-MKL non coding scores: https://zenodo.org/records/3981121
GREEN-DB constraint scores¶
GREEN-DB is a comprehensive collection of 2.4 million regulatory elements in the human genome collected from previously published databases, high-throughput screenings and functional studies. This plugin annotates the constrain scores only, and is build on top of the GREEN-DB bed files ( GRCh38): https://zenodo.org/records/5636209 GREEN-DB constrains scores are annotated per region type: enhancers, promotors, bivalent, insulators, silencers. If multiple regions of the same type overlap, VIP annotates the highest constraint score.
APOGEE 2¶
APOGEE-2 predicts pathogenicity scores for missense mitochondrial variants. A custom APOGEE VEP plugin annotates mitochondrial variants with computed APOGEE scores.
MitoTIP¶
MitoTIP predicts pathogenicity scores for mtDNA tRNA variants. A custom MitoTIP VEP plugin annotates mitochondrial variants with computed mitoTip scores and their corresponding quartiles (Q1-Q4).
HmtVar¶
HmtVar contains disease scores for mtDNA SNVs. A custom HmtVar VEP plugin annotates mitochondrial tRNA variants with computed disease scores.
BRAIN-MAGNET¶
BRAIN-MAGNET predictions for all possible SNPs from NSC NCREs (~100 million), you can easily score your interested variants from our pre-scored data. Please note that this plugin is not enabled by default. It can be added through the "params.vcf.vep_additional_plugins" configuration option. Resources for this plugin should be provided by the user and are not part of the VIP install script. The resources can be found here: resources