rs4147539

chr4-99316322-GTTC-Gchr4-99316322-GTTC-GTTCTTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000668.6(ADH1B):c.260-23_260-21del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 1,605,764 control chromosomes in the GnomAD database, including 8,919 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.096 (1008 hom., cov: 31)
  • Exomes 𝑓: 0.090 (7911 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6	c.260-23_260-21del		intron_variant		ENST00000305046.13
ADH1B	NM_001286650.2	c.140-23_140-21del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13	c.260-23_260-21del		intron_variant		1	NM_000668.6	P1

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14529 AN: 152130 Hom.: 1001 Cov.: 31

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0966

GnomAD3 exomes AF: 0.119 AC: 29615 AN: 249342 Hom.: 3129 AF XY: 0.107 AC XY: 14437 AN XY: 135004

Gnomad AFR exome AF: 0.0666

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.0893

Gnomad EAS exome AF: 0.0763

Gnomad SAS exome AF: 0.0454

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0831

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0900 AC: 130748 AN: 1453516 Hom.: 7911 AF XY: 0.0876 AC XY: 63386 AN XY: 723572

Gnomad4 AFR exome AF: 0.0670

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.0848

Gnomad4 EAS exome AF: 0.0760

Gnomad4 SAS exome AF: 0.0476

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.0830

Gnomad4 OTH exome AF: 0.0856

GnomAD4 genome AF: 0.0956 AC: 14553 AN: 152248 Hom.: 1008 Cov.: 31 AF XY: 0.100 AC XY: 7478 AN XY: 74440

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.0979

Alfa AF: 0.0843 Hom.: 131

Bravo AF: 0.106

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs4147539; hg19: chr4-100237479;