ClinVar

Description

Variant summary: CFTR c.1209+6A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 249772 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1209+6A>G in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported. However, a database, sickkids, reports that this mutation "was found in anItalian adult patient with idiopatic infertility; moreover detected in a 50 years old Italian man, also carrying R31C, with BPCO, Bronchiectasis, lung infection by Pseudomonas aeruginosa and sweat chloride 36mEq/l. He is PS." A ClinVar submission (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.