chr12-111804401-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000690.4(ALDH2):​c.1521+428G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 152,236 control chromosomes in the GnomAD database, including 1,475 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.071 ( 1475 hom., cov: 31)

Consequence

ALDH2
NM_000690.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.840

Publications

5 publications found
Variant links:
Genes affected
ALDH2 (HGNC:404): (aldehyde dehydrogenase 2 family member) This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Nov 2016]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALDH2NM_000690.4 linkc.1521+428G>A intron_variant Intron 12 of 12 ENST00000261733.7 NP_000681.2 P05091-1A0A384NPN7
ALDH2NM_001204889.2 linkc.1380+428G>A intron_variant Intron 11 of 11 NP_001191818.1 P05091-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALDH2ENST00000261733.7 linkc.1521+428G>A intron_variant Intron 12 of 12 1 NM_000690.4 ENSP00000261733.2 P05091-1
ALDH2ENST00000416293.7 linkc.1380+428G>A intron_variant Intron 11 of 11 2 ENSP00000403349.3 P05091-2
ALDH2ENST00000548536.1 linkn.*1397+428G>A intron_variant Intron 13 of 13 3 ENSP00000448179.1 F8VSB0
ALDH2ENST00000549106.1 linkn.*100+428G>A intron_variant Intron 3 of 3 3 ENSP00000474669.1 S4R3S4

Frequencies

GnomAD3 genomes
AF:
0.0705
AC:
10721
AN:
152118
Hom.:
1478
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.147
Gnomad ASJ
AF:
0.00548
Gnomad EAS
AF:
0.612
Gnomad SAS
AF:
0.0960
Gnomad FIN
AF:
0.00207
Gnomad MID
AF:
0.0538
Gnomad NFE
AF:
0.00344
Gnomad OTH
AF:
0.0712
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0706
AC:
10744
AN:
152236
Hom.:
1475
Cov.:
31
AF XY:
0.0771
AC XY:
5738
AN XY:
74434
show subpopulations
African (AFR)
AF:
0.107
AC:
4426
AN:
41534
American (AMR)
AF:
0.148
AC:
2253
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00548
AC:
19
AN:
3468
East Asian (EAS)
AF:
0.612
AC:
3154
AN:
5154
South Asian (SAS)
AF:
0.0967
AC:
467
AN:
4830
European-Finnish (FIN)
AF:
0.00207
AC:
22
AN:
10628
Middle Eastern (MID)
AF:
0.0578
AC:
17
AN:
294
European-Non Finnish (NFE)
AF:
0.00344
AC:
234
AN:
68032
Other (OTH)
AF:
0.0719
AC:
152
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
399
798
1197
1596
1995
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
110
220
330
440
550
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0327
Hom.:
54
Bravo
AF:
0.0871
Asia WGS
AF:
0.251
AC:
872
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.41
DANN
Benign
0.89
PhyloP100
-0.84
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs2158029; hg19: chr12-112242205; API