Submissions for variant NM_005502.4(ABCA1):c.2320A>C (p.Thr774Pro)

gnomAD frequency: 0.00289  dbSNP: rs35819696

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000263472	SCV000476296	benign	Hypoalphalipoproteinemia, primary, 1	2018-01-13	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	RCV000318710	SCV000476297	uncertain significance	Tangier disease	2018-01-13	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590520	SCV000698588	benign	not provided	2016-12-05	criteria provided, single submitter	clinical testing	Variant summary: The ABCA1 c.2320A>C (p.Thr774Pro) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant. This variant was found in 201/121258 control chromosomes (1 homozygote) at a frequency of 0.0016576, which is approximately 133 times the estimated maximal expected allele frequency of a pathogenic ABCA1 variant (0.0000125), suggesting this variant is likely a benign polymorphism. This variant has been shown to not be associated with lipid levels or CAD phenotype (Clee_2001). Further evidence toward benign classification is that one internal sample carries this variant and LDLR c.1291G>A (pathogenic). In addition, the cholesterol efflux was within the normal range in cells from two individuals who had this variant (Cohen_2004). Taken together, this variant is classified as benign.
GeneDx	RCV000590520	SCV001814305	likely benign	not provided	2021-04-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 11238261, 24497850, 15297675)
Invitae	RCV000590520	SCV002390011	benign	not provided	2024-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002446622	SCV002733525	likely benign	Cardiovascular phenotype	2020-11-25	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.
New York Genome Center	RCV002467766	SCV002764305	uncertain significance	Hypoalphalipoproteinemia, primary, 1; Tangier disease	2021-07-02	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001700361	SCV001923232	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000590520	SCV001973803	likely benign	not provided		no assertion criteria provided	clinical testing