rs13134764

Variant names:

• chr4-99291016-A-T
• rs13134764
• ENST00000500358.6:n.4160+68A>T

Variant summary

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

The ENST00000908169.1(ADH1A):​c.-102T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,277,528 control chromosomes in the GnomAD database, including 39,512 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 0.27 (6877 hom., cov: 31)
  • Exomes 𝑓: 0.29 (32635 hom.)
• Consequence: ADH1A ENST00000908169.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 10 publications found

Genes affected

ENSG00000246090 (HGNC:):

ADH1A (HGNC:249): (alcohol dehydrogenase 1A (class I), alpha polypeptide) This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence. [provided by RefSeq, Nov 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908169.1. 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
	LOC100507053	NR_037884.1		n.4160+68A>T		intron	N/A
	ADH1A	NM_000667.4	MANE Select	c.-102T>A		upstream_gene	N/A	NP_000658.1	P07327

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.4160+68A>T		intron	N/A
	ADH1A	ENST00000908169.1		c.-102T>A		5_prime_UTR	Exon 1 of 10	ENSP00000578228.1
	ADH1A	ENST00000908168.1		c.-102T>A		5_prime_UTR	Exon 1 of 9	ENSP00000578227.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41492 AN: 151126 Hom.: 6881 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0338

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.294 AC: 331578 AN: 1126286 Hom.: 32635 Cov.: 15 AF XY: 0.292 AC XY: 166820 AN XY: 571770

African (AFR) AF: 0.0791 AC: 2112 AN: 26706

American (AMR) AF: 0.168 AC: 6130 AN: 36500

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 8349 AN: 21568

East Asian (EAS) AF: 0.0225 AC: 851 AN: 37888

South Asian (SAS) AF: 0.157 AC: 11541 AN: 73356

European-Finnish (FIN) AF: 0.310 AC: 15524 AN: 50002

Middle Eastern (MID) AF: 0.314 AC: 1555 AN: 4956

European-Non Finnish (NFE) AF: 0.328 AC: 271622 AN: 826878

Other (OTH) AF: 0.287 AC: 13894 AN: 48432

GnomAD4 genome AF: 0.274 AC: 41493 AN: 151242 Hom.: 6877 Cov.: 31 AF XY: 0.267 AC XY: 19727 AN XY: 73856

African (AFR) AF: 0.101 AC: 4154 AN: 41324

American (AMR) AF: 0.264 AC: 4004 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1596 AN: 3456

East Asian (EAS) AF: 0.0339 AC: 175 AN: 5164

South Asian (SAS) AF: 0.159 AC: 762 AN: 4802

European-Finnish (FIN) AF: 0.338 AC: 3506 AN: 10386

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26078 AN: 67662

Other (OTH) AF: 0.329 AC: 688 AN: 2094

Alfa AF: 0.156 Hom.: 346

Bravo AF: 0.262

Asia WGS AF: 0.0990 AC: 349 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		0.24
PromoterAI		-0.027	Neutral
Mutation Taster		=300/0	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: rs13134764; hg19: chr4-100212173;