Submissions for variant NM_000071.3(CBS):c.531+11G>A

gnomAD frequency: 0.00479  dbSNP: rs186114513

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124146	SCV000167560	benign	not specified	2013-01-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000124146	SCV000268834	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	531+11G>A in intron 6 of CBS: This variant is not expected to have clinical sign ificance because it is not located within the conserved splice consensus sequenc e. It has been identified in 0.7% (62/8578) of European American chromosomes fro m a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washin gton.edu/EVS; dbSNP rs186114513).
Illumina Laboratory Services, Illumina	RCV000625490	SCV000436226	benign	Classic homocystinuria	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001795224	SCV001158768	likely benign	not provided	2023-09-13	criteria provided, single submitter	clinical testing
Invitae	RCV002228266	SCV001719170	benign	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345430	SCV002640701	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2015-09-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000124146	SCV004029470	benign	not specified	2023-07-30	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000625490	SCV000745586	likely benign	Classic homocystinuria	2017-01-23	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000124146	SCV001918012	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001795224	SCV002036454	likely benign	not provided		no assertion criteria provided	clinical testing