rs1229983

chr4-99318845-T-C

Variant summary

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

The NM_000668.6(ADH1B):c.60A>G(p.Lys20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,612,808 control chromosomes in the GnomAD database, including 1,439 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 0.042 (155 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1284 hom.)
• Consequence: ADH1B NM_000668.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.214 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6	c.60A>G	p.Lys20=	synonymous_variant	2/9	ENST00000305046.13
ADH1B	NM_001286650.2	c.-61A>G		5_prime_UTR_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13	c.60A>G	p.Lys20=	synonymous_variant	2/9	1	NM_000668.6	P1

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6330 AN: 152082 Hom.: 155 Cov.: 33

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0446 AC: 11216 AN: 251260 Hom.: 338 AF XY: 0.0429 AC XY: 5832 AN XY: 135792

Gnomad AFR exome AF: 0.0439

Gnomad AMR exome AF: 0.0785

Gnomad ASJ exome AF: 0.0342

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0541

Gnomad FIN exome AF: 0.0632

Gnomad NFE exome AF: 0.0363

Gnomad OTH exome AF: 0.0482

GnomAD4 exome AF: 0.0378 AC: 55213 AN: 1460608 Hom.: 1284 Cov.: 30 AF XY: 0.0380 AC XY: 27597 AN XY: 726650

Gnomad4 AFR exome AF: 0.0464

Gnomad4 AMR exome AF: 0.0775

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0522

Gnomad4 FIN exome AF: 0.0648

Gnomad4 NFE exome AF: 0.0350

Gnomad4 OTH exome AF: 0.0372

GnomAD4 genome AF: 0.0416 AC: 6335 AN: 152200 Hom.: 155 Cov.: 33 AF XY: 0.0423 AC XY: 3145 AN XY: 74414

Gnomad4 AFR AF: 0.0445

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0546

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.0365

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0382 Hom.: 60

Bravo AF: 0.0427

Asia WGS AF: 0.0380 AC: 132 AN: 3478

EpiCase AF: 0.0314

EpiControl AF: 0.0331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	5.7
Dann	Benign	0.72

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: rs1229983; hg19: chr4-100240002;