NM_000690.4:c.441-1194G>A

Variant names:

• chr12-111788629-G-A
• rs10849970
• NM_000690.4:c.441-1194G>A

Variant summary

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

The NM_000690.4(ALDH2):​c.441-1194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 152,242 control chromosomes in the GnomAD database, including 1,224 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 0.052 (1224 hom., cov: 31)
• Consequence: ALDH2 NM_000690.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH2	NM_000690.4	MANE Select	c.441-1194G>A		intron	N/A	NP_000681.2
	ALDH2	NM_001204889.2		c.300-1194G>A		intron	N/A	NP_001191818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH2	ENST00000261733.7	TSL:1 MANE Select	c.441-1194G>A		intron	N/A	ENSP00000261733.2
	ENSG00000257767	ENST00000546840.3	TSL:5	c.429-1194G>A		intron	N/A	ENSP00000450353.4
	ALDH2	ENST00000871406.1		c.552-1194G>A		intron	N/A	ENSP00000541465.1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7870 AN: 152124 Hom.: 1229 Cov.: 31

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0517 AC: 7874 AN: 152242 Hom.: 1224 Cov.: 31 AF XY: 0.0575 AC XY: 4277 AN XY: 74426

African (AFR) AF: 0.0527 AC: 2190 AN: 41544

American (AMR) AF: 0.106 AC: 1621 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.619 AC: 3189 AN: 5156

South Asian (SAS) AF: 0.0993 AC: 479 AN: 4824

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10626

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00315 AC: 214 AN: 68024

Other (OTH) AF: 0.0592 AC: 125 AN: 2112

Alfa AF: 0.0251 Hom.: 241

Bravo AF: 0.0642

Asia WGS AF: 0.249 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.48
PhyloP100		0.13
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: rs10849970; hg19: chr12-112226433;