chr9-104831048-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PP3_StrongPP5_Moderate
The NM_005502.4(ABCA1):c.1769G>T(p.Trp590Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,613,612 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 Likely pathogenic (★).
Frequency
Consequence
NM_005502.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCA1 | ENST00000374736.8 | c.1769G>T | p.Trp590Leu | missense_variant | Exon 14 of 50 | 1 | NM_005502.4 | ENSP00000363868.3 | ||
ABCA1 | ENST00000678995.1 | c.1769G>T | p.Trp590Leu | missense_variant | Exon 14 of 50 | ENSP00000504612.1 |
Frequencies
GnomAD3 genomes AF: 0.0000659 AC: 10AN: 151748Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251454Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135900
GnomAD4 exome AF: 0.000129 AC: 189AN: 1461864Hom.: 0 Cov.: 36 AF XY: 0.000122 AC XY: 89AN XY: 727232
GnomAD4 genome AF: 0.0000659 AC: 10AN: 151748Hom.: 0 Cov.: 29 AF XY: 0.0000945 AC XY: 7AN XY: 74082
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Published functional studies demonstrate a damaging effect: normal to reduced cell surface expression, but defective cholesterol efflux activity as compared to wild type (Cohen et al., 2004; Kiss et al., 2007; Sadananda et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35974019, 25215231, 36088354, 15297675, 17303779, 17113061, 15262183, 28870971, 29150341, 32041611, 31980526, 26255038, 30333156, 12407001) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at