ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3854C>T (p.Ala1285Val) (rs397508617)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000585919 SCV000696994 uncertain significance not specified 2019-01-11 criteria provided, single submitter clinical testing Variant summary: CFTR c.3854C>T (p.Ala1285Val) results in a non-conservative amino acid change located in the AAA+ ATPase domain (IPR003593) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0006 in 276564 control chromosomes (gnomAD and publication data), predominantly within the South Asian subpopulation at a frequency of 0.0053 in the gnomAD database, including 1 homozygote. This frequency is not higher than expected for a pathogenic variant in CFTR causing Congenital Bilateral Absence of the Vas Deferens (CBAVD) (0.0053 vs 0.013), allowing no conclusion about variant significance. The variant, c.3854C>T, has been reported in the literature in a compound heterozygous Asian Indian individual affected with CBAVD who also carried the variant c.1001+11C>T (Sachdeva 2011). The variant was also found during carrier screening in homozygosity in an Asian Indian (Schwartz 2009) and an Australian individual (Archibald 2017), however the phenotype was not specified in these cases. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577447 SCV000679387 not provided Cystic fibrosis no assertion provided literature only

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.