12-111783212-C-A
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000690.4(ALDH2):c.274C>A(p.Pro92Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000624 in 1,613,488 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00068 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00062 ( 9 hom. )
Consequence
ALDH2
NM_000690.4 missense
NM_000690.4 missense
Scores
2
4
12
Clinical Significance
Conservation
PhyloP100: 3.78
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 made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.013536364).
BP6
Variant 12-111783212-C-A is Benign according to our data. Variant chr12-111783212-C-A is described in ClinVar as [Benign]. Clinvar id is 779154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000619 (904/1461128) while in subpopulation AMR AF= 0.0193 (863/44656). AF 95% confidence interval is 0.0183. There are 9 homozygotes in gnomad4_exome. There are 367 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALDH2 | NM_000690.4 | c.274C>A | p.Pro92Thr | missense_variant | 3/13 | ENST00000261733.7 | NP_000681.2 | |
ALDH2 | NM_001204889.2 | c.219+1190C>A | intron_variant | NP_001191818.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALDH2 | ENST00000261733.7 | c.274C>A | p.Pro92Thr | missense_variant | 3/13 | 1 | NM_000690.4 | ENSP00000261733 | P1 | |
ALDH2 | ENST00000416293.7 | c.219+1190C>A | intron_variant | 2 | ENSP00000403349 | |||||
ALDH2 | ENST00000548536.1 | c.*150C>A | 3_prime_UTR_variant, NMD_transcript_variant | 4/14 | 3 | ENSP00000448179 |
Frequencies
GnomAD3 genomes AF: 0.000677 AC: 103AN: 152242Hom.: 1 Cov.: 32
GnomAD3 genomes
AF:
AC:
103
AN:
152242
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00307 AC: 768AN: 250046Hom.: 9 AF XY: 0.00217 AC XY: 294AN XY: 135266
GnomAD3 exomes
AF:
AC:
768
AN:
250046
Hom.:
AF XY:
AC XY:
294
AN XY:
135266
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000619 AC: 904AN: 1461128Hom.: 9 Cov.: 31 AF XY: 0.000505 AC XY: 367AN XY: 726804
GnomAD4 exome
AF:
AC:
904
AN:
1461128
Hom.:
Cov.:
31
AF XY:
AC XY:
367
AN XY:
726804
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000676 AC: 103AN: 152360Hom.: 1 Cov.: 32 AF XY: 0.000671 AC XY: 50AN XY: 74510
GnomAD4 genome
AF:
AC:
103
AN:
152360
Hom.:
Cov.:
32
AF XY:
AC XY:
50
AN XY:
74510
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
288
Asia WGS
AF:
AC:
4
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D
REVEL
Benign
Sift
Benign
.;D
Sift4G
Benign
T;T
Polyphen
0.019
.;B
Vest4
0.41
MVP
MPC
0.44
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at