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GeneBe

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

Scores

7
5
4

Clinical Significance

drug response reviewed by expert panel P:1B:1O:5

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
ALDH2NM_000690.4 linkuse as main transcriptc.1510G>A p.Glu504Lys missense_variant 12/13 ENST00000261733.7
ALDH2NM_001204889.2 linkuse as main transcriptc.1369G>A p.Glu457Lys missense_variant 11/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALDH2ENST00000261733.7 linkuse as main transcriptc.1510G>A p.Glu504Lys missense_variant 12/131 NM_000690.4 P1P05091-1
ALDH2ENST00000416293.7 linkuse as main transcriptc.1369G>A p.Glu457Lys missense_variant 11/122 P05091-2
ALDH2ENST00000548536.1 linkuse as main transcriptc.*1386G>A 3_prime_UTR_variant, NMD_transcript_variant 13/143
ALDH2ENST00000549106.1 linkuse as main transcriptc.*89G>A 3_prime_UTR_variant, NMD_transcript_variant 3/43

Frequencies

GnomAD3 genomes
AF:
0.00787
AC:
1196
AN:
152056
Hom.:
141
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000918
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.225
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00527
GnomAD3 exomes
AF:
0.0189
AC:
4582
AN:
242666
Hom.:
590
AF XY:
0.0176
AC XY:
2310
AN XY:
131478
show subpopulations
Gnomad AFR exome
AF:
0.000194
Gnomad AMR exome
AF:
0.000390
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.254
Gnomad SAS exome
AF:
0.000270
Gnomad FIN exome
AF:
0.0000471
Gnomad NFE exome
AF:
0.0000274
Gnomad OTH exome
AF:
0.00555
GnomAD4 exome
AF:
0.00695
AC:
10123
AN:
1456236
Hom.:
1239
AF XY:
0.00689
AC XY:
4989
AN XY:
724228
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.000318
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.246
Gnomad4 SAS exome
AF:
0.000222
Gnomad4 FIN exome
AF:
0.0000377
Gnomad4 NFE exome
AF:
0.0000361
Gnomad4 OTH exome
AF:
0.00586
Alfa
AF:
0.00605
Hom.:
219
Bravo
AF:
0.00896
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.00104
AC:
4
ExAC
AF:
0.0165
AC:
2006
Asia WGS
AF:
0.0290
AC:
102
AN:
3478

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 providedliterature onlyOMIMFeb 01, 2010- -
Alcohol dependence Benign:1
protective, no assertion criteria providedliterature onlyOMIMFeb 01, 2010- -
Esophageal cancer, alcohol-related, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMFeb 01, 2010- -
Susceptibility to hangover Other:1
risk factor, no assertion criteria providedliterature onlyOMIMFeb 01, 2010- -
Alcohol sensitivity, acute Other:1
drug response, no assertion criteria providedliterature onlyOMIMFeb 12, 2021- -
Sublingual nitroglycerin, susceptibility to poor response to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMFeb 01, 2010- -
ethanol response - Toxicity Other:1
drug response, reviewed by expert panelcurationPharmGKBMar 24, 2021PharmGKB 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Pathogenic
0.22
Cadd
Pathogenic
32
Dann
Pathogenic
1.0
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.87
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.99
D;D
MetaRNN
Benign
0.0019
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.5e-7
P;P;P;P
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Uncertain
0.60
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.018
D;D
Polyphen
0.96
.;D
Vest4
0.48
MPC
1.0
ClinPred
0.10
T
GERP RS
6.0
Varity_R
0.95
gMVP
0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs671; hg19: chr12-112241766; COSMIC: COSV55665271; COSMIC: COSV55665271;