List RVIS¶

Command examples:¶

atav.sh --list-rvis --variant PATH_TO_YOUR_VARIANT_FILE --out PATH_TO_OUTPUT_DIR

Command options:¶

--list-rvis: trigger list rvis function.

--variant: use a variant id file (one id per line) or a variant id list (comma delimited)

id format: chr-pos-ref-alt

Output:¶

rvis.csv

• Variant ID
• Gene Name
• IGM-Roche-Avg%GeneCov "A population averaged estimate of the percentage of the protein-coding sequence for a gene that's covered with atleast 10-fold coverage across IGM sequenced exomes (Roche kit)".

A higher estimate indicates the better the protein-coding sequence of the gene is captured (on average) using the Roche kit.

• 0.1%RVIS[EVS] "EVS-based RVIS as published in PLoS Genetics paper (Petrovski et al. 2013)"
• 0.1%RVIS%[EVS] "EVS-based RVIS percentile as published in PLoS Genetics paper (Petrovski et al. 2013)"

As published, a lower RVIS and percentile score indicates a gene is increasingly intolerant relative to the rest of the assessed human protein-coding genes

• EdgeCase[EVS] "Indicator that there was little resolution based on EVS data to confidently asses intolerance (See: http://genic-intolerance.org/about.jsp)"

Given the EVS cohort and protein-coding gene size some genes (Edge Case genes) have insufficient resolution data to be confident of their RVIS. For these genes, we recommend considering their OERatio as an alternative estimate of their genic intolerance.

• OEratio%tile[EVS] "Alternative EVS-based genic intolerance score for EdgeCase genes flagged by indicator as Y (See: http://genic-intolerance.org/about.jsp)"
• GenicConstraint[EVS] "EVS-based Constraint (missense z) scores as published in the Nature Genetics paper (Samocha et al. 2014)"

A percentile estimate of how constrained the gene is relative to the rest of the protein-coding exome.

• 1.0%ncRVIS[IGM] "IGM WGS-based noncoding RVIS (ncRVIS) reflecting a gene's 5', 3' and promoter sequence intolerance to variation (Petrovski et al. 2015 [26332131])"
• 1.0%ncRVIS%tile[IGM] "IGM WGS-based noncoding RVIS (ncRVIS) percentile reflecting a gene's 5', 3' and promoter sequence intolerance to variation (Petrovski et al. 2015 [26332131])"

A percentile estimate of how intolerant the noncoding exome sequence of a protein-coding gene is relative to the noncoding sequence of other protein-coding genes. Lower ncRVIS and percentile indicate increasingly intolerant noncoding (UTR and 250bp promoter) sequence. Genes with intolerant noncoding sequence have been described as begin dosage-sensitive genes.

• ncGERP "GERP++ based non-coding genic conservation score reflecting the average GERP++ score for a protein-coding gene's noncoding exome sequence + 250bp promoter (Petrovski et al. 2015 [26332131])"
• ncGERP%tile "GERP++ based non-coding genic conservation percentile reflecting how conserved a protein-coding gene's noncoding exome sequence + 250bp promoter is based on all protein-coding genes (Petrovski et al. 2015 [26332131])"

A percentile estimate of how overall conserved the noncoding exome sequence of a protein-coding gene is relative to the noncoding sequence of other protein-coding genes. Higher ncGERP scores and lower ncGERP percentiles indicate increasingly conserved noncoding (UTR and 250bp promoter) sequence. Genes with highly conserved noncoding sequence have been described as begin dosage-sensitive genes.

• pcGERP "GERP++ based protein-coding genic conservation score reflecting the average GERP++ score for a protein-coding gene's coding sequence is (Petrovski et al. 2015 [26332131])"
• pcGERP%tile "GERP++ based protein-coding genic conservation percentile reflecting how conserved a protein-coding gene's coding sequence is based on all protein-coding genes (Petrovski et al. 2015 [26332131])"

A percentile estimate of how overall conserved the protein-coding exome sequence of a gene is relative to the protein-coding sequence of other genes. Higher pcGERP scores and lower pcGERP percentiles indicate increasingly conserved protein-coding genes.

• 0.05%_anypopn_RVIS[ExAC] "ExAC-based RVIS as published online (Contact: sp3347@cumc.columbia.edu; See: http://genic-intolerance.org/)"
• 0.05%_anypopn_RVIS%tile[ExAC] "ExAC-based RVIS percentile as published online (Contact: sp3347@cumc.columbia.edu; See: http://genic-intolerance.org/)"

The RVIS has been reformulated using the ExAC cohort (accessed: January 13th 2015 [updated scores for release0.3]). Note, in addition to using a larger population of sequenced samples, this updated genic score differs from the original implementation in three major ways: the 'common' MAF is assigned as 0.05% and the score now leverages the stratified ethnicity data provided within ExAC. Moreover, X chromosome genes are assessed independently of the autosomal genes.

• OEratio%tile[ExAC] "Alternative ExAC-based genic intolerance score for EdgeCase genes flagged by indicator as Y"

An OEratio, as previously described, now constructed on the ExAC cohort.

• GenicConstraint_mis-z[ExAC] "ExAC-based Constraint missense z-scores as published online on the ExAC Server [accessed February 2016] (ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3/functional_gene_constraint/)"
• GenicConstraint_mis-z%tile[ExAC] "ExAC-based Constraint missense z-score percentiles generated from the GenicConstraint_mis-z[ExAC]"
• LoF-FDRLoF[EVS] "A loss-of-function depletion score generated to find genes that are specifically depleted of LoF genetic variation using the EVS reference cohort (Petrovski et al. 2015 [26332131])"
• LoF-FDRLoF[ExAC] "A loss-of-function depletion score generated to find genes that are specifically depleted of LoF genetic variation using the ExAC reference cohort (details: http://genic-intolerance.org/about.jsp)"
• LoF-pLI[ExAC] "ExAC-based probability of being loss-of-function intolerant (intolerant of both heterozygous and homozygous lof variants). [accessed February 2016] See: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3/functional_gene_constraint/README_fordist_cleaned_exac_r03_z_data_pLI_2016_01_13.txt"
• LoF-pRec[ExAC] "ExAC-based probability of being intolerant of homozygous, but not heterozygous lof variants. [accessed February 2016] See: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3/functional_gene_constraint/README_fordist_cleaned_exac_r03_z_data_pLI_2016_01_13.txt"
• LoF-pNull[ExAC] "ExAC-based probability of being TOLERANT of both heterozygous and homozygous lof variants. [accessed February 2016] See: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3/functional_gene_constraint/README_fordist_cleaned_exac_r03_z_data_pLI_2016_01_13.txt"

For additional details, please check RVIS