rs187652566
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BS1BS2_Supporting
The NM_005502.4(ABCA1):c.2660G>T(p.Cys887Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000398 in 1,614,030 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005502.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCA1 | ENST00000374736.8 | c.2660G>T | p.Cys887Phe | missense_variant | Exon 19 of 50 | 1 | NM_005502.4 | ENSP00000363868.3 | ||
ABCA1 | ENST00000678995.1 | c.2660G>T | p.Cys887Phe | missense_variant | Exon 19 of 50 | ENSP00000504612.1 |
Frequencies
GnomAD3 genomes AF: 0.000407 AC: 62AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000461 AC: 116AN: 251376Hom.: 0 AF XY: 0.000449 AC XY: 61AN XY: 135862
GnomAD4 exome AF: 0.000397 AC: 580AN: 1461758Hom.: 2 Cov.: 31 AF XY: 0.000369 AC XY: 268AN XY: 727186
GnomAD4 genome AF: 0.000407 AC: 62AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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Has been reported in individuals with increased HDL-cholesterol and decreased total cholesterol levels (Hu et al., 2009; Service et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20800056, 24497850, 19743957, 32041611) -
Hypercholesterolemia, familial, 1 Uncertain:1
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Cardiovascular phenotype Benign:1
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. -
Tangier disease Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Hypoalphalipoproteinemia, primary, 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at