4-99313896-A-G

Position:

• chr4-99313896-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000668.6(ADH1B):​c.753T>C​(p.Ile251Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 1,612,934 control chromosomes in the GnomAD database, including 542,042 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 0.81 (50000 hom., cov: 31)
  • Exomes 𝑓: 0.82 (492042 hom.)
• Consequence: ADH1B NM_000668.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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]

ADH1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.008 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.753T>C	p.Ile251Ile	synonymous_variant	6/9	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.633T>C	p.Ile211Ile	synonymous_variant	7/10		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.753T>C	p.Ile251Ile	synonymous_variant	6/9	1	NM_000668.6	ENSP00000306606.8

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123131 AN: 151960 Hom.: 49954 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.926

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.826

GnomAD3 exomes AF: 0.815 AC: 204755 AN: 251142 Hom.: 83848 AF XY: 0.814 AC XY: 110499 AN XY: 135734

Gnomad AFR exome AF: 0.765

Gnomad AMR exome AF: 0.793

Gnomad ASJ exome AF: 0.844

Gnomad EAS exome AF: 0.918

Gnomad SAS exome AF: 0.748

Gnomad FIN exome AF: 0.800

Gnomad NFE exome AF: 0.831

Gnomad OTH exome AF: 0.824

GnomAD4 exome AF: 0.820 AC: 1198119 AN: 1460856 Hom.: 492042 Cov.: 95 AF XY: 0.820 AC XY: 595568 AN XY: 726744

Gnomad4 AFR exome AF: 0.765

Gnomad4 AMR exome AF: 0.798

Gnomad4 ASJ exome AF: 0.845

Gnomad4 EAS exome AF: 0.921

Gnomad4 SAS exome AF: 0.756

Gnomad4 FIN exome AF: 0.809

Gnomad4 NFE exome AF: 0.825

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.810 AC: 123230 AN: 152078 Hom.: 50000 Cov.: 31 AF XY: 0.808 AC XY: 60038 AN XY: 74336

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.822

Alfa AF: 0.828 Hom.: 16533

Bravo AF: 0.812

Asia WGS AF: 0.767 AC: 2663 AN: 3476

EpiCase AF: 0.834

EpiControl AF: 0.840

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.7
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1789882; hg19: chr4-100235053;