9-104798503-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BP6
The NM_005502.4(ABCA1):c.5039G>A(p.Arg1680Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000518 in 1,614,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCA1 | ENST00000374736.8 | c.5039G>A | p.Arg1680Gln | missense_variant | Exon 37 of 50 | 1 | NM_005502.4 | ENSP00000363868.3 | ||
ABCA1 | ENST00000678995.1 | c.5045G>A | p.Arg1682Gln | missense_variant | Exon 37 of 50 | ENSP00000504612.1 |
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152112Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000326 AC: 82AN: 251314Hom.: 0 AF XY: 0.000339 AC XY: 46AN XY: 135816
GnomAD4 exome AF: 0.000540 AC: 790AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.000512 AC XY: 372AN XY: 727244
GnomAD4 genome AF: 0.000302 AC: 46AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74436
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
- -
- -
not specified Benign:1
Variant summary: ABCA1 c.5039G>A (p.Arg1680Gln) results in a conservative amino acid change located in the ABC-2 type transporter, transmembrane domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00034 in 266804 control chromosomes, predominantly at a frequency of 0.00055 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 55 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCA1 causing Familial Hypoalphalipoproteinemia phenotype (1e-05). c.5039G>A has been reported in the literature in individuals with both high and low level of HDL-C, all without strong evidence for causality (e.g.Cohen_2004, Berge_2010, Sadananda_2015, Peloso_2016, Abdel-Razek_2018, Dong_2022). These reports do not provide unequivocal conclusions about association of the variant with Familial Hypoalphalipoproteinemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15297675, 24497850, 26350511, 26255038, 29150341, 35460704, 20800056). ClinVar contains an entry for this variant (Variation ID: 364394). Based on the evidence outlined above, the variant was classified as likely 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at