Submissions for variant NM_005502.4(ABCA1):c.3159T>G (p.Val1053=)

gnomAD frequency: 0.00751  dbSNP: rs35871586

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000332729	SCV000476277	benign	Tangier disease	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.
Illumina Laboratory Services, Illumina	RCV000373336	SCV000476278	benign	Hypoalphalipoproteinemia, primary, 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590431	SCV000698591	benign	not provided	2016-05-30	criteria provided, single submitter	clinical testing	Variant summary: The ABCA1 c.3159T>G (p.Val1053Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 918/121410 control chromosomes (including 6 homozygotes) at a frequency of 0.0075612, which is approximately 605 times the estimated maximal expected allele frequency of a pathogenic ABCA1 variant (0.0000125), suggesting this variant is a benign polymorphism. One internal sample carrying this variant also carries another deleterious variant PCSK9 p.Tyr142X further supporting for benign outcome. Taken together, this variant is classified as Benign.
Invitae	RCV000590431	SCV001110195	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000590431	SCV001814952	likely benign	not provided	2020-07-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002323566	SCV002610162	benign	Cardiovascular phenotype	2019-09-10	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
CeGaT Center for Human Genetics Tuebingen	RCV000590431	SCV003917684	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	ABCA1: BP4, BP7, BS1, BS2