Submissions for variant NM_024649.5(BBS1):c.24T>C (p.Asp8=)

gnomAD frequency: 0.00267  dbSNP: rs55848325

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000173529	SCV000224650	benign	not specified	2015-06-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226235	SCV000290794	benign	Bardet-Biedl syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000709651	SCV000743594	benign	Bardet-Biedl syndrome 1	2015-02-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000173529	SCV000918631	benign	not specified	2018-09-10	criteria provided, single submitter	clinical testing	Variant summary: BBS1 c.24T>C alters a non-conserved nucleotide resulting in a synonymous change. 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 0.0039 in 276810 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 4-fold of the estimated maximal expected allele frequency for a pathogenic variant in BBS1 causing Bardet-Biedl Syndrome phenotype (0.00094), strongly suggesting that the variant is benign. The variant, c.24T>C, has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (Gerth_2008, Deveault_2011, Hichri_2005) but in some cases not all BBS genes were tested. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services, Illumina	RCV000709651	SCV001261225	likely benign	Bardet-Biedl syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genetic Services Laboratory, University of Chicago	RCV000173529	SCV002066205	likely benign	not specified	2017-09-25	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000709651	SCV002764597	uncertain significance	Bardet-Biedl syndrome 1	2021-03-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003407641	SCV004136980	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	BBS1: BP4, BP7, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV003407641	SCV005214325	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003891704	SCV000314361	benign	BBS1-related disorder	2023-11-21	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000709651	SCV000745742	likely benign	Bardet-Biedl syndrome 1	2017-04-19	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000709651	SCV001454307	benign	Bardet-Biedl syndrome 1	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000173529	SCV001924631	benign	not specified		no assertion criteria provided	clinical testing