rs2276332

chr4-99282290-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000667.4(ADH1A):c.828+56T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 1,613,972 control chromosomes in the GnomAD database, including 9,161 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 0.092 (983 hom., cov: 32)
  • Exomes 𝑓: 0.091 (8178 hom.)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1A	NM_000667.4	c.828+56T>G		intron_variant		ENST00000209668.3
LOC100507053	NR_037884.1	n.3790-4505A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1A	ENST00000209668.3	c.828+56T>G		intron_variant		1	NM_000667.4	P1
	ENST00000500358.6	n.3790-4505A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14051 AN: 152140 Hom.: 978 Cov.: 32

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0805

Gnomad OTH AF: 0.0917

GnomAD3 exomes AF: 0.120 AC: 29926 AN: 250290 Hom.: 3253 AF XY: 0.108 AC XY: 14622 AN XY: 135380

Gnomad AFR exome AF: 0.0560

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.0876

Gnomad EAS exome AF: 0.0805

Gnomad SAS exome AF: 0.0457

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0847

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0912 AC: 133255 AN: 1461714 Hom.: 8178 Cov.: 31 AF XY: 0.0889 AC XY: 64654 AN XY: 727156

Gnomad4 AFR exome AF: 0.0561

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.0829

Gnomad4 EAS exome AF: 0.0775

Gnomad4 SAS exome AF: 0.0481

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.0848

Gnomad4 OTH exome AF: 0.0848

GnomAD4 genome AF: 0.0924 AC: 14073 AN: 152258 Hom.: 983 Cov.: 32 AF XY: 0.0969 AC XY: 7215 AN XY: 74430

Gnomad4 AFR AF: 0.0554

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.0893

Gnomad4 SAS AF: 0.0599

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0806

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.0879 Hom.: 720

Bravo AF: 0.102

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2276332; hg19: chr4-100203447; COSMIC: COSV52924343; COSMIC: COSV52924343;