ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.2988+1G>T

dbSNP: rs75096551
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780170 SCV000917218 likely pathogenic not specified 2017-11-30 criteria provided, single submitter clinical testing Variant summary: The CFTR c.2988+1G>T variant (also known as 3120+1G>T) involves the alteration of a conserved intronic nucleotide and 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 276728 control chromosomes (gnomAD). Even though this variant has been reported in multiple affected CF pts across ethnicities (Watson_2004 and Palomaki_2004), the exact nature of nucleotide change in those reports is suspicious. To our knowledge, the variant of interest has not been cited by reputable databases and/or clinical diagnostic laboratories. Although, another variant at this position, c.2988+1G>A, has been highly reported as a common pathogenic mutation. Taken together, this variant is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV002535668 SCV003456382 pathogenic Cystic fibrosis 2024-12-19 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 18 of the CFTR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with cystic fibrosis (PMID: 15371902, 23974870). ClinVar contains an entry for this variant (Variation ID: 632766). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005036112 SCV005666398 likely pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation 2024-01-23 criteria provided, single submitter clinical testing

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.