rs4147536

Positions:

• chr4-99317955-A-C
• chr4-99317955-A-G
• chr4-99317955-A-T

Variant summary

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

The NM_000668.6(ADH1B):​c.259+91T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,564,178 control chromosomes in the GnomAD database, including 470,080 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 0.72 (40239 hom., cov: 32)
  • Exomes 𝑓: 0.78 (429841 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

Genes affected

ADH1B (HGNC:250): (alcohol dehydrogenase 1B (class I), beta polypeptide) The protein encoded by this gene is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This encoded protein, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6	c.259+91T>G		intron_variant		ENST00000305046.13
ADH1B	NM_001286650.2	c.139+91T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13	c.259+91T>G		intron_variant		1	NM_000668.6	P1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109442 AN: 151954 Hom.: 40229 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.746

GnomAD4 exome AF: 0.778 AC: 1099060 AN: 1412106 Hom.: 429841 Cov.: 31 AF XY: 0.778 AC XY: 543532 AN XY: 698510

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.806

Gnomad4 EAS exome AF: 0.921

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.745

Gnomad4 NFE exome AF: 0.789

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.720 AC: 109494 AN: 152072 Hom.: 40239 Cov.: 32 AF XY: 0.718 AC XY: 53340 AN XY: 74300

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.742

Alfa AF: 0.779 Hom.: 54086

Bravo AF: 0.714

Asia WGS AF: 0.717 AC: 2490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.49
DANN	Benign	0.42

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: rs4147536; hg19: chr4-100239112;