12-111790445-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_000690.4(ALDH2):c.564G>A(p.Pro188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,614,090 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.00057 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 5 hom. )
Consequence
ALDH2
NM_000690.4 synonymous
NM_000690.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.34
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 12-111790445-G-A is Benign according to our data. Variant chr12-111790445-G-A is described in ClinVar as [Benign]. Clinvar id is 3035849.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-2.34 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ALDH2 | NM_000690.4 | c.564G>A | p.Pro188= | synonymous_variant | 6/13 | ENST00000261733.7 | NP_000681.2 | |
| ALDH2 | NM_001204889.2 | c.423G>A | p.Pro141= | synonymous_variant | 5/12 | NP_001191818.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ALDH2 | ENST00000261733.7 | c.564G>A | p.Pro188= | synonymous_variant | 6/13 | 1 | NM_000690.4 | ENSP00000261733 | P1 | |
| ALDH2 | ENST00000416293.7 | c.423G>A | p.Pro141= | synonymous_variant | 5/12 | 2 | ENSP00000403349 | |||
| ALDH2 | ENST00000548536.1 | c.*440G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/14 | 3 | ENSP00000448179 |
Frequencies
GnomAD3 genomes 0.000565 AC: 86AN: 152090Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000875 AC: 220AN: 251452Hom.: 1 AF XY: 0.000795 AC XY: 108AN XY: 135902
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GnomAD4 exome AF: 0.000482 AC: 704AN: 1461882Hom.: 5 Cov.: 31 AF XY: 0.000485 AC XY: 353AN XY: 727244
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GnomAD4 genome 0.000565 AC: 86AN: 152208Hom.: 1 Cov.: 32 AF XY: 0.000484 AC XY: 36AN XY: 74400
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
ALDH2-related disorder Benign:1
| Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 29, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at