Variant 4-99311547-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000668.6(ADH1B):c.938G>A(p.Arg313His) variant causes a missense change. The variant allele was found at a frequency of 0.00065 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

ADH1B
NM_000668.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

Variant links:

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]

ADH1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26114607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6 linkuse as main transcript	c.938G>A	p.Arg313His	missense_variant	7/9	ENST00000305046.13
ADH1B	NM_001286650.2 linkuse as main transcript	c.818G>A	p.Arg273His	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13 linkuse as main transcript	c.938G>A	p.Arg313His	missense_variant	7/9	1	NM_000668.6	P1	P00325-1
ADH1B	ENST00000625860.2 linkuse as main transcript	c.818G>A	p.Arg273His	missense_variant	7/9	1			P00325-2
ADH1B	ENST00000506651.5 linkuse as main transcript	c.818G>A	p.Arg273His	missense_variant	8/10	2			P00325-2
ADH1B	ENST00000515694.4 linkuse as main transcript	n.3033G>A		non_coding_transcript_exon_variant	7/9	2

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000406

AC:

102

AN:

251288

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000801

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000681

AC:

995

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000648

AC XY:

471

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.000853

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000355

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000681

Hom.:

Bravo

AF:

0.000363

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000328

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.938G>A (p.R313H) alteration is located in exon 7 (coding exon 7) of the ADH1B gene. This alteration results from a G to A substitution at nucleotide position 938, causing the arginine (R) at amino acid position 313 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.012

.;T;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

.;D;.;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.80

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.4

D;.;.;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.027

D;.;.;.

Sift4G

Uncertain

0.028

D;D;D;.

Vest4

0.73

MVP

0.44

MPC

0.77

ClinPred

0.15

GERP RS

3.7

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over