rs13134764

Positions:

• chr4-99291016-A-T

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.4160+68A>T variant causes a intron 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: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.4160+68A>T		intron_variant
ADH1A	NM_000667.4	c.-102T>A		upstream_gene_variant		ENST00000209668.3	NP_000658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3	c.-102T>A		upstream_gene_variant		1	NM_000667.4	ENSP00000209668.2

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

Gnomad4 AFR exome AF: 0.0791

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.0225

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.287

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

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.0339

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.329

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.70

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: rs13134764; hg19: chr4-100212173;