ClinVar

Description

A Heterozygous Frameshift variant c.1029delC in Exon 8 of the CFTR gene that results in the premature termination of the protein (p.Cys343fs*1) was identified. The observed variant has a minor allele frequency of 0.00006% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl 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. 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. The variant was found in ClinVar (Variant ID :53170) with a classification of Pathogenic and a review status of (3 star) criteria provided, expert panel reviewed. The variant was previously reported by Malone G et al.,1998. Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.