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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000668.6(ADH1B):c.938G>T(p.Arg313Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ADH1B
NM_000668.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6 link	c.938G>T	p.Arg313Leu	missense_variant	Exon 7 of 9	ENST00000305046.13	NP_000659.2	P00325-1V9HW50
ADH1B	NM_001286650.2 link	c.818G>T	p.Arg273Leu	missense_variant	Exon 8 of 10		NP_001273579.1	P00325-2D6RHZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADH1B	ENST00000305046.13 link	c.938G>T	p.Arg313Leu	missense_variant	Exon 7 of 9	1	NM_000668.6	ENSP00000306606.8	P00325-1
ADH1B	ENST00000625860.2 link	c.818G>T	p.Arg273Leu	missense_variant	Exon 7 of 9	1		ENSP00000486614.1	P00325-2D6RHZ6
ADH1B	ENST00000506651.5 link	c.818G>T	p.Arg273Leu	missense_variant	Exon 8 of 10	2		ENSP00000425998.2	P00325-2D6RHZ6
ADH1B	ENST00000515694.4 link	n.3033G>T		non_coding_transcript_exon_variant	Exon 7 of 9	2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251288

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000308

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000217

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

.;T;T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

.;D;.;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.73

D;D;D;D

MetaSVM

Benign

-0.89

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.6

D;.;.;.

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;.

Vest4

0.93

MutPred

0.76

Loss of MoRF binding (P = 0.0107);.;.;Loss of MoRF binding (P = 0.0107);

MVP

0.44

MPC

0.71

ClinPred

0.74

GERP RS

3.7

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over