NM_000690.4:c.115-5263G>T

Variant names:

• chr12-111776655-G-T
• rs2238152
• NM_000690.4:c.115-5263G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000690.4(ALDH2):​c.115-5263G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,878 control chromosomes in the GnomAD database, including 2,498 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 (2498 hom., cov: 31)
• Consequence: ALDH2 NM_000690.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 15 publications found

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]

ENSG00000257767 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000690.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH2	NM_000690.4	MANE Select	c.115-5263G>T		intron	N/A	NP_000681.2
	ALDH2	NM_001204889.2		c.115-5263G>T		intron	N/A	NP_001191818.1	P05091-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH2	ENST00000261733.7	TSL:1 MANE Select	c.115-5263G>T		intron	N/A	ENSP00000261733.2	P05091-1
	ENSG00000257767	ENST00000546840.3	TSL:5	c.103-5263G>T		intron	N/A	ENSP00000450353.4	F8VP50
	ALDH2	ENST00000871406.1		c.225+935G>T		intron	N/A	ENSP00000541465.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27090 AN: 151760 Hom.: 2500 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0912

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27086 AN: 151878 Hom.: 2498 Cov.: 31 AF XY: 0.177 AC XY: 13140 AN XY: 74226

African (AFR) AF: 0.199 AC: 8257 AN: 41404

American (AMR) AF: 0.174 AC: 2650 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 316 AN: 3464

East Asian (EAS) AF: 0.234 AC: 1210 AN: 5166

South Asian (SAS) AF: 0.212 AC: 1020 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10516

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11438 AN: 67956

Other (OTH) AF: 0.186 AC: 391 AN: 2106

Alfa AF: 0.179 Hom.: 297

Bravo AF: 0.182

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.65
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2238152; hg19: chr12-112214459;