ClinVar

Description

Variant summary: CFTR c.4242+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: one predict the variant abolishes a 5 prime splicing donor site; two predict the variant weakens a 5 prime donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250474 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4242+5G>A has been reported in the literature in one individual affected with Cystic Fibrosis. This report does not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.