Submissions for variant NM_024649.5(BBS1):c.378G>A (p.Leu126=)

gnomAD frequency: 0.21158  dbSNP: rs2298806

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000247494	SCV000314362	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000709660	SCV000373261	benign	Bardet-Biedl syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics Inc	RCV000709660	SCV000677145	benign	Bardet-Biedl syndrome 1	2017-06-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589192	SCV000699515	benign	not provided	2016-11-15	criteria provided, single submitter	clinical testing	Variant summary: The BBS1 c.378G>A (p.Leu126Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a polymorphism outcome for this variant along with 5/5 splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 27024/121032 control chromosomes (3285 homozygotes) at a frequency of 0.2232798, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic BBS1 variant (0.0009449), suggesting this variant is likely a benign polymorphism. A clinical diagnostic laboratory and at least one publication classified this variant as benign. Taken together, this variant is classified as benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000709660	SCV000744898	benign	Bardet-Biedl syndrome 1	2015-09-21	criteria provided, single submitter	clinical testing
Invitae	RCV000262515	SCV001000097	benign	Bardet-Biedl syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000709660	SCV001755022	benign	Bardet-Biedl syndrome 1	2021-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000589192	SCV001960515	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003888663	SCV004707602	benign	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000709660	SCV000733085	benign	Bardet-Biedl syndrome 1		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000709660	SCV001454309	benign	Bardet-Biedl syndrome 1	2020-09-16	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000247494	SCV001951940	benign	not specified		no assertion criteria provided	clinical testing