ClinVar

Description

Variant summary: The CFTR c.3139+18C>T variant involves the alteration of a non-conserved intronic nucleotide. 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 0.0014 in 276326 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (0.0014 vs 0.013), allowing no conclusion about variant significance. The c.3139+18C>T has been reported in the literature in an individual presented with mild Cystic Fibrosis, however this patient was compound heterozygous for two deleterious CFTR variants, c.1083delG (p.Trp361fsX8) and c.2291delG (p.Arg764fsX7), suggesting the variant of interest to be in the benign spectrum (Romey_1994). In addition, the variant was found in trans with F508del in an individual, who did not have CF (Gamaletsou_2017). 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 benign. Multiple published reports cite the variant as "polymorphism" (Bombier_1998; Romey_1994; Pignatti_1995). Based on the evidence outlined above, the variant was classified as benign.