4-99317841-T-C

Position:

• chr4-99317841-T-C

Variant summary

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

The NM_000668.6(ADH1B):​c.259+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 731,672 control chromosomes in the GnomAD database, including 41,932 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 (6155 hom., cov: 32)
  • Exomes 𝑓: 0.32 (35777 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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 = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.259+205A>G		intron_variant		ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.139+205A>G		intron_variant			NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.259+205A>G		intron_variant		1	NM_000668.6	ENSP00000306606	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37784 AN: 151954 Hom.: 6164 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.321 AC: 186184 AN: 579600 Hom.: 35777 Cov.: 8 AF XY: 0.329 AC XY: 98451 AN XY: 299210

Gnomad4 AFR exome AF: 0.0996

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.248 AC: 37766 AN: 152072 Hom.: 6155 Cov.: 32 AF XY: 0.252 AC XY: 18712 AN XY: 74350

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.256

Alfa AF: 0.295 Hom.: 14344

Bravo AF: 0.237

Asia WGS AF: 0.477 AC: 1654 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	1.1
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2075633; hg19: chr4-100238998;