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GeneBe

rs77121243

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000690.4(ALDH2):c.682-261T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,936 control chromosomes in the GnomAD database, including 2,533 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 0.18 ( 2533 hom., cov: 31)

Consequence

ALDH2
NM_000690.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.706
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALDH2NM_000690.4 linkuse as main transcriptc.682-261T>C intron_variant ENST00000261733.7
ALDH2NM_001204889.2 linkuse as main transcriptc.541-261T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALDH2ENST00000261733.7 linkuse as main transcriptc.682-261T>C intron_variant 1 NM_000690.4 P1P05091-1
ALDH2ENST00000416293.7 linkuse as main transcriptc.541-261T>C intron_variant 2 P05091-2
ALDH2ENST00000548536.1 linkuse as main transcriptc.*558-261T>C intron_variant, NMD_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.179
AC:
27183
AN:
151816
Hom.:
2535
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.200
Gnomad AMI
AF:
0.146
Gnomad AMR
AF:
0.174
Gnomad ASJ
AF:
0.0911
Gnomad EAS
AF:
0.234
Gnomad SAS
AF:
0.212
Gnomad FIN
AF:
0.152
Gnomad MID
AF:
0.275
Gnomad NFE
AF:
0.169
Gnomad OTH
AF:
0.189
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.179
AC:
27179
AN:
151936
Hom.:
2533
Cov.:
31
AF XY:
0.178
AC XY:
13191
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.200
Gnomad4 AMR
AF:
0.174
Gnomad4 ASJ
AF:
0.0911
Gnomad4 EAS
AF:
0.234
Gnomad4 SAS
AF:
0.211
Gnomad4 FIN
AF:
0.152
Gnomad4 NFE
AF:
0.169
Gnomad4 OTH
AF:
0.185
Alfa
AF:
0.173
Hom.:
3022
Bravo
AF:
0.182
Asia WGS
AF:
0.247
AC:
858
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
4.1
Dann
Benign
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs441; hg19: chr12-112228849; API