rs2066701

chr4-99317256-G-Achr4-99317256-G-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+790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,028 control chromosomes in the GnomAD database, including 6,160 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 0.25 (6160 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6	c.259+790C>T		intron_variant		ENST00000305046.13
ADH1B	NM_001286650.2	c.139+790C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13	c.259+790C>T		intron_variant		1	NM_000668.6	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37834 AN: 151910 Hom.: 6169 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.256

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.249 AC: 37814 AN: 152028 Hom.: 6160 Cov.: 32 AF XY: 0.252 AC XY: 18711 AN XY: 74286

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.255

Alfa AF: 0.275 Hom.: 3649

Bravo AF: 0.238

Asia WGS AF: 0.476 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.7
Dann	Benign	0.44

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: rs2066701; hg19: chr4-100238413;