chr12-111789919-C-T

Variant names:

• chr12-111789919-C-T
• rs201725825
• NM_000690.4:c.537C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_000690.4(ALDH2):​c.537C>T​(p.Cys179Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: ALDH2 NM_000690.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.365
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 12-111789919-C-T is Benign according to our data. Variant chr12-111789919-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 743525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.365 with no splicing effect.

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.537C>T	p.Cys179Cys	synonymous	Exon 5 of 13	NP_000681.2
	ALDH2	NM_001204889.2		c.396C>T	p.Cys132Cys	synonymous	Exon 4 of 12	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.537C>T	p.Cys179Cys	synonymous	Exon 5 of 13	ENSP00000261733.2	P05091-1
	ENSG00000257767	ENST00000546840.3	TSL:5	c.525C>T	p.Cys175Cys	synonymous	Exon 6 of 8	ENSP00000450353.4	F8VP50
	ALDH2	ENST00000871406.1		c.648C>T	p.Cys216Cys	synonymous	Exon 6 of 14	ENSP00000541465.1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000175 AC: 44 AN: 251248 AF XY: 0.000140

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000435 AC: 636 AN: 1461744 Hom.: 0 Cov.: 31 AF XY: 0.000389 AC XY: 283 AN XY: 727178

African (AFR) AF: 0.000239 AC: 8 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86244

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.000520 AC: 578 AN: 1111932

Other (OTH) AF: 0.000729 AC: 44 AN: 60388

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17 AN XY: 74338

African (AFR) AF: 0.000265 AC: 11 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000441 Hom.: 0

Bravo AF: 0.000374

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	2.3
DANN	Benign	0.83
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs201725825; hg19: chr12-112227723;