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REVEL

REVEL is an ensemble method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. REVEL was trained using recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. When applied to two independent test sets, REVEL had the best overall performance (p<10-12) compared with any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies <0.5%. Compared with other ensemble methods, the area under the receiver operating characteristic curve (AUC) for REVEL was 0.046-0.182 higher in an independent test set of 935 recent SwissVar disease variants and 123,935 putatively neutral exome sequencing variants, and 0.027-0.143 higher in an independent test set of 1953 pathogenic and 2406 benign variants recently reported in ClinVar. We provide precomputed REVEL scores for all possible human missense variants to facilitate the identification of pathogenic variants in the sea of rare variants discovered as sequencing studies expand in scale.

More details, check: https://sites.google.com/site/revelgenomics/