REVEL (Rare Exome Variant Ensemble Learner)

Overview

REVEL is an ensemble method for predicting the pathogenicity of missense variants, combining scores from 13 individual tools (including MutPred, FATHMM, VEST3, PolyPhen-2, SIFT, CADD, DANN, MetaSVM, MetaLR, MutationAssessor, MutationTaster, LRT, and GERP++) using a random forest classifier. It was trained on rare missense variants from ClinVar disease mutations versus common non-disease variants. Scores range from 0 to 1, with higher scores indicating greater predicted pathogenicity.

Used by

• Applied to score somatic variants in endometrial polyps; UBE2A p.(Arg6Trp) received a REVEL score of 0.56, contributing to its multi-tool functional characterization as a likely driver alteration PMID:28445112

Notes

• Pre-computed scores available for all possible human missense SNVs via the REVEL database.
• Scores >0.5 are associated with pathogenicity in most calibration studies.
• Ensemble approach leverages complementary strengths of 13 underlying tools.

Sources

• PMID:28445112

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