rs671
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000690(ALDH2):c.1510G>A(p.Glu504Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00787 in 152056 control chromosomes in the gnomAD Genomes database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).
Frequency
Genomes: 𝑓 0.0079 ( 141 hom., cov: 31)
Exomes 𝑓: 0.019 ( 590 hom. )
Consequence
ALDH2
NM_000690 missense
NM_000690 missense
Scores
7
5
4
Clinical Significance
Conservation
PhyloP100: 9.78
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.001886636).
BA1
?
GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH2 | NM_000690.4 | c.1510G>A | p.Glu504Lys | missense_variant | 12/13 | ENST00000261733.7 | |
ALDH2 | NM_001204889.2 | c.1369G>A | p.Glu457Lys | missense_variant | 11/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH2 | ENST00000261733.7 | c.1510G>A | p.Glu504Lys | missense_variant | 12/13 | 1 | NM_000690.4 | P1 | |
ALDH2 | ENST00000416293.7 | c.1369G>A | p.Glu457Lys | missense_variant | 11/12 | 2 | |||
ALDH2 | ENST00000548536.1 | c.*1386G>A | 3_prime_UTR_variant, NMD_transcript_variant | 13/14 | 3 | ||||
ALDH2 | ENST00000549106.1 | c.*89G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00787 AC: 1196AN: 152056Hom.: 141 Cov.: 31
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GnomAD3 exomes AF: 0.0189 AC: 4582AN: 242666Hom.: 590 AF XY: 0.0176 AC XY: 2310AN XY: 131478
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GnomAD4 exome AF: 0.00695 AC: 10123AN: 1456236Hom.: 1239 AF XY: 0.00689 AC XY: 4989AN XY: 724228
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ClinVar
Significance: drug response
Submissions summary: Pathogenic:1Benign:1Other:5
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
AMED syndrome, digenic Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2010 | - - |
Alcohol dependence Benign:1
protective, no assertion criteria provided | literature only | OMIM | Feb 01, 2010 | - - |
Esophageal cancer, alcohol-related, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Feb 01, 2010 | - - |
Susceptibility to hangover Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Feb 01, 2010 | - - |
Alcohol sensitivity, acute Other:1
drug response, no assertion criteria provided | literature only | OMIM | Feb 12, 2021 | - - |
Sublingual nitroglycerin, susceptibility to poor response to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Feb 01, 2010 | - - |
ethanol response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 2B: Variants in Level 2B clinical annotations are not in PharmGKB’s Tier 1 VIPs. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2B clinical annotations must be supported by at least two independent publications. Drug-variant association: Toxicity |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.96
.;D
Vest4
MPC
1.0
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at