Gene metrics
The Gene metrics card helps you assess whether a gene is tolerant or intolerant to variation. It includes:
Intolerance metrics from ExAC and gnomAD that relate to gene constraint and variant burden
Direct links to ExAC and gnomAD for quick access
Resources field (v100.39.0+) with links to external gene databases offering detailed information on gene function and clinical relevance:
ClinGen gene
DECIPHER gene
GenCC
OMIM gene
Metrics and interpretation
pLI = p(LoF intolerant) is a probability of being loss-of-function intolerant to heterozygous and homozygous LoF variants.
Scale:
🔴 pLI ≥ 0.9: extremely LoF intolerant,
🟠 pLI > 0.1 & < 0.9: intermediate value,
🟢 pLI ≤ 0.1: LoF tolerant.
The missense Z-score indicates intolerance to missense variants based on the deviation of observed missense variants versus the expected number.
Scale:
🔴 Missense Z ≥ 3: missense intolerant,
🟠 Missense Z > 2.5 & < 3: intermediate value,
🟢 Missense Z ≤ 2.5: missense tolerant.
p(REC) is a probability of being intolerant to homozygous, but not heterozygous LoF.
Scale:
🔴 p(REC) ≥ 0.8: Hom LoF intolerant,
🟠 p(REC) > 0.2 & < 0.8: intermediate value,
🟢 p(REC) ≤ 0.2: Hom LoF tolerant.
RVIS = Residual Variation Intolerance Score is indicative of a gene's intolerance to functional variation based on comparing the overall number of observed variants in a gene to the observed common functional variants.
Scale:
🔴 RVIS ≤ 30: functional variation intolerant,
🟠 RVIS > 30 & < 50: intermediate value,
🟢 RVIS ≥ 50: functional variation tolerant.
O/E Score is the ratio of the observed/expected number of LoF variants. It is a continuous measure of gene tolerance to LoF variation that incorporates a 90% confidence interval. The closer the O/E is to zero, the more likely the gene is LoF-constrained. If a hard threshold is needed for the interpretation of Mendelian disease cases, use the upper bound of the O/E confidence interval < 0.35.
Note: Gene metrics card is not available for CNVs or mtDNA variants.
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