rs2066714
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005502.4(ABCA1):āc.2649A>Gā(p.Ile883Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,613,862 control chromosomes in the GnomAD database, including 33,696 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I883V) has been classified as Likely benign.
Frequency
Consequence
NM_005502.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA1 | NM_005502.4 | c.2649A>G | p.Ile883Met | missense_variant | 18/50 | ENST00000374736.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA1 | ENST00000374736.8 | c.2649A>G | p.Ile883Met | missense_variant | 18/50 | 1 | NM_005502.4 | P1 | |
ABCA1 | ENST00000678995.1 | c.2649A>G | p.Ile883Met | missense_variant | 18/50 |
Frequencies
GnomAD3 genomes ? AF: 0.254 AC: 38593AN: 151990Hom.: 7177 Cov.: 32
GnomAD3 exomes AF: 0.211 AC: 53126AN: 251362Hom.: 9257 AF XY: 0.198 AC XY: 26918AN XY: 135866
GnomAD4 exome AF: 0.158 AC: 230954AN: 1461756Hom.: 26500 Cov.: 33 AF XY: 0.156 AC XY: 113725AN XY: 727188
GnomAD4 genome ? AF: 0.254 AC: 38670AN: 152106Hom.: 7196 Cov.: 32 AF XY: 0.253 AC XY: 18846AN XY: 74366
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 21, 2018 | This variant is associated with the following publications: (PMID: 24466114, 31006134, 26243156, 27884173, 10431237, 21300560, 11238261, 17951323, 17923263) - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2019 | 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. - |
Tangier disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at