ClinVar Miner

Submissions for variant NM_024649.5(BBS1):c.951+1G>C

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
Neuberg Centre For Genomic Medicine, NCGM RCV003338232 SCV004047269 uncertain significance Bardet-Biedl syndrome 1 criteria provided, single submitter clinical testing The splice site c.951+1G>C variant has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. But, a different splice site variant (c.951+1G>A) has been reported in individuals affected with Bardet-Biedl syndrome 1 (Mary L et al., 2019; Forsythe E., et al). It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Donor and acceptor splice site variants typically lead to a loss of protein function (Baralle D et al., 2005), and loss-of-function variants in BBS1 are known to be pathogenic (Mykytyn K et al., 2002). The variant is novel (not in any individuals) in 1000 Genomes and in 0.00039% alleles in heterozygous state in gnomAD. The nucleotide change in BBS1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003633707 SCV004558106 pathogenic Bardet-Biedl syndrome 2023-03-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12920096, 21344540, 27659767). This variant is present in population databases (rs746875134, gnomAD 0.007%). This sequence change affects a donor splice site in intron 10 of the BBS1 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 BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803).

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.