ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.1780-1G>T

dbSNP: rs104886338
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
Genetic Diagnostic Laboratory, University of Szeged RCV000207547 SCV000262767 pathogenic X-linked Alport syndrome 2016-02-02 criteria provided, single submitter clinical testing
Invitae RCV001384768 SCV001584414 pathogenic not provided 2020-04-29 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL4A5 are known to be pathogenic (PMID: 9195222, 10752524, 14514738, 24854265, 26809805). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with Alport syndrome (PMID: 26934356, 16941480, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 222057). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 24 of the COL4A5 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
PreventionGenetics, part of Exact Sciences RCV003417753 SCV004109594 pathogenic COL4A5-related condition 2023-05-23 criteria provided, single submitter clinical testing The COL4A5 c.1780-1G>T variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been observed to segregate in three female family members with hematuria and/or thin basement membrane nephropathy (Kovács et al 2016. PubMed ID: 26934356). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice acceptor site in COL4A5 are expected to be pathogenic. This variant is interpreted as pathogenic.

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.