rs4147531

Variant names:

• chr4-99291040-G-A
• rs4147531
• ENST00000500358.6:n.4160+92G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-99291040-G-A
• chr4-99291040-G-T

Variant summary

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

The ENST00000908168.1(ADH1A):​c.-126C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 949,306 control chromosomes in the GnomAD database, including 88,908 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 0.39 (12645 hom., cov: 31)
  • Exomes 𝑓: 0.42 (76263 hom.)
• Consequence: ADH1A ENST00000908168.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 13 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908168.1. 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+92G>A		intron	N/A
	ADH1A	NM_000667.4	MANE Select	c.-126C>T		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+92G>A		intron	N/A
	ADH1A	ENST00000908168.1		c.-126C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000578227.1
	ADH1A	ENST00000908167.1		c.-126C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000578226.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59174 AN: 151532 Hom.: 12643 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.419 AC: 334225 AN: 797656 Hom.: 76263 Cov.: 10 AF XY: 0.412 AC XY: 172722 AN XY: 418848

African (AFR) AF: 0.224 AC: 4520 AN: 20190

American (AMR) AF: 0.543 AC: 19362 AN: 35674

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 10598 AN: 19378

East Asian (EAS) AF: 0.0956 AC: 3494 AN: 36560

South Asian (SAS) AF: 0.221 AC: 14176 AN: 64022

European-Finnish (FIN) AF: 0.481 AC: 23593 AN: 49014

Middle Eastern (MID) AF: 0.431 AC: 1875 AN: 4354

European-Non Finnish (NFE) AF: 0.453 AC: 240515 AN: 530372

Other (OTH) AF: 0.422 AC: 16092 AN: 38092

GnomAD4 genome AF: 0.390 AC: 59210 AN: 151650 Hom.: 12645 Cov.: 31 AF XY: 0.387 AC XY: 28647 AN XY: 74102

African (AFR) AF: 0.233 AC: 9654 AN: 41392

American (AMR) AF: 0.511 AC: 7782 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1889 AN: 3468

East Asian (EAS) AF: 0.115 AC: 594 AN: 5156

South Asian (SAS) AF: 0.217 AC: 1040 AN: 4798

European-Finnish (FIN) AF: 0.481 AC: 5032 AN: 10470

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31719 AN: 67832

Other (OTH) AF: 0.439 AC: 925 AN: 2108

Alfa AF: 0.450 Hom.: 26518

Bravo AF: 0.390

Asia WGS AF: 0.226 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.39
PhyloP100		-1.4
PromoterAI		0.017	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4147531; hg19: chr4-100212197; COSMIC: COSV52925045;