chr9-104800523-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005502.4(ABCA1):āc.4760A>Gā(p.Lys1587Arg) variant causes a missense change. The variant allele was found at a frequency of 0.725 in 1,612,774 control chromosomes in the GnomAD database, including 437,586 homozygotes. In-silico tool predicts 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. K1587Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_005502.4 missense
Scores
Clinical Significance
Conservation
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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.4760A>G | p.Lys1587Arg | missense_variant | 35/50 | ENST00000374736.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA1 | ENST00000374736.8 | c.4760A>G | p.Lys1587Arg | missense_variant | 35/50 | 1 | NM_005502.4 | P1 | |
ABCA1 | ENST00000678995.1 | c.4766A>G | p.Lys1589Arg | missense_variant | 35/50 |
Frequencies
GnomAD3 genomes AF: 0.604 AC: 91783AN: 151968Hom.: 32186 Cov.: 32
GnomAD3 exomes AF: 0.707 AC: 177856AN: 251394Hom.: 65969 AF XY: 0.710 AC XY: 96531AN XY: 135872
GnomAD4 exome AF: 0.738 AC: 1078212AN: 1460688Hom.: 405398 Cov.: 41 AF XY: 0.737 AC XY: 535261AN XY: 726734
GnomAD4 genome AF: 0.604 AC: 91810AN: 152086Hom.: 32188 Cov.: 32 AF XY: 0.612 AC XY: 45483AN XY: 74354
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2018 | This variant is associated with the following publications: (PMID: 29083407, 28008009, 15520867, 20346718, 22929031) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Tangier disease Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | 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. - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2018 | 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. - |
Hypoalphalipoproteinemia, primary, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at