4-99307788-T-C

Position:

• chr4-99307788-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.*52A>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 0.093 in 1,596,822 control chromosomes in the GnomAD database, including 9,301 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 0.097 (1046 hom., cov: 32)
  • Exomes 𝑓: 0.093 (8255 hom.)
• Consequence: ADH1B NM_000668.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.*52A>G		3_prime_UTR_variant	9/9	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.*52A>G		3_prime_UTR_variant	10/10		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.*52A>G		3_prime_UTR_variant	9/9	1	NM_000668.6	ENSP00000306606	P1
ADH1B	ENST00000625860.2	c.*52A>G		3_prime_UTR_variant	9/9	1		ENSP00000486614
ADH1B	ENST00000506651.5	c.*52A>G		3_prime_UTR_variant	10/10	2		ENSP00000425998
ADH1B	ENST00000515694.4	n.3275A>G		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14779 AN: 152084 Hom.: 1039 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.0886

Gnomad SAS AF: 0.0587

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.0982

GnomAD4 exome AF: 0.0925 AC: 133643 AN: 1444618 Hom.: 8255 Cov.: 29 AF XY: 0.0902 AC XY: 64884 AN XY: 719728

Gnomad4 AFR exome AF: 0.0690

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.0850

Gnomad4 EAS exome AF: 0.0763

Gnomad4 SAS exome AF: 0.0489

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.0858

Gnomad4 OTH exome AF: 0.0872

GnomAD4 genome AF: 0.0973 AC: 14804 AN: 152204 Hom.: 1046 Cov.: 32 AF XY: 0.102 AC XY: 7593 AN XY: 74414

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.0884

Gnomad4 SAS AF: 0.0596

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.0995

Alfa AF: 0.0900 Hom.: 455

Bravo AF: 0.108

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.53

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: rs17033; hg19: chr4-100228945;