Submissions for variant NM_005502.4(ABCA1):c.634T>A (p.Ser212Thr)

gnomAD frequency: 0.00424  dbSNP: rs115216814

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589515	SCV000698596	benign	not provided	2016-05-31	criteria provided, single submitter	clinical testing	Variant summary: The ABCA1 c.634T>A (p.Ser212Thr) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a benign outcome. This variant was found in 156/141780 control chromosomes (including one homozygote), predominantly observed in the African subpopulation at a frequency of 0.0138382 (144/10406). This frequency is about 1107 times the estimated maximal expected allele frequency of a pathogenic ABCA1 variant (0.0000125), suggesting this is a benign polymorphism found primarily in the populations of African origin. 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.
Illumina Laboratory Services, Illumina	RCV001167050	SCV001329490	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	RCV001167051	SCV001329491	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000589515	SCV001720673	benign	not provided	2025-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000589515	SCV001780507	likely benign	not provided	2019-09-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000589515	SCV006077346	likely benign	not provided	2025-04-01	criteria provided, single submitter	clinical testing	ABCA1: BP4, BS1
PreventionGenetics, part of Exact Sciences	RCV004530645	SCV004748451	benign	ABCA1-related disorder	2019-06-04	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).