4-99307309-T-C

Position:

• chr4-99307309-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.*531A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 155,136 control chromosomes in the GnomAD database, including 6,284 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 (6167 hom., cov: 32)
  • Exomes 𝑓: 0.23 (117 hom.)
• Consequence: ADH1B NM_000668.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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	Protein	UniProt
ADH1B	NM_000668.6	c.*531A>G		3_prime_UTR_variant	9/9	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.*531A>G		3_prime_UTR_variant	10/10		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046	c.*531A>G		3_prime_UTR_variant	9/9	1	NM_000668.6	ENSP00000306606.8
ADH1B	ENST00000625860	c.*531A>G		3_prime_UTR_variant	9/9	1		ENSP00000486614.1
ADH1B	ENST00000515694.4	n.3754A>G		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37856 AN: 152060 Hom.: 6176 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.235 AC: 695 AN: 2958 Hom.: 117 Cov.: 0 AF XY: 0.253 AC XY: 364 AN XY: 1438

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.249 AC: 37836 AN: 152178 Hom.: 6167 Cov.: 32 AF XY: 0.252 AC XY: 18731 AN XY: 74420

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.255

Alfa AF: 0.294 Hom.: 9530

Bravo AF: 0.238

Asia WGS AF: 0.476 AC: 1651 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	2.6
DANN	Benign	0.58

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: rs1042026; hg19: chr4-100228466;