ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1920T>C (p.Phe640=) (rs145877746)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000242518 SCV000304477 likely benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725286 SCV000335702 uncertain significance not provided 2018-02-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000725286 SCV000602986 benign not provided 2018-05-16 criteria provided, single submitter clinical testing
Invitae RCV000630468 SCV000751426 likely benign Cystic fibrosis 2017-08-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000242518 SCV000919151 benign not specified 2018-02-21 criteria provided, single submitter clinical testing Variant summary: CFTR c.1920T>C alters a non-conserved nucleotide resulting in a synonymous change (p.Phe640=). 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 4.7e-05 in 276596 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (4.7e-05 vs 0.013), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1920T>C in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported via publications. The variant was reported in the databases to be present on the same allele as a complex pathogenic allele (c.220C>T_c.601G>A_c.3808G>A). In addition, our laboratory has identified the variant in numerous (>20) individuals with the same pathogenic complex allele, and in several of these cases a second pathogenic CFTR variant was also identified (e.g. p.Phe508del (in 2 cases), p.Ile507del (in one case), p.Arg1162X (in one case), c.5T_TG12 (in one case)). These co-occurrences with other pathogenic variants provide supporting evidence for a benign role. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, where one laboratory classified the variant as benign, and the other laboratory as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.