Variant rs6413413 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000668.6(ADH1B):c.178A>T(p.Thr60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,613,824 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0071 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 79 hom. )

Consequence

ADH1B
NM_000668.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.83

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034271777).

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6 linkuse as main transcript	c.178A>T	p.Thr60Ser	missense_variant	3/9	ENST00000305046.13
ADH1B	NM_001286650.2 linkuse as main transcript	c.58A>T	p.Thr20Ser	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13 linkuse as main transcript	c.178A>T	p.Thr60Ser	missense_variant	3/9	1	NM_000668.6	P1	P00325-1

Frequencies

GnomAD3 genomes

AF:

0.00712

AC:

1081

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000919

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00461

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0437

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00707

Gnomad OTH

AF:

0.00672

GnomAD3 exomes

AF:

0.00757

AC:

1902

AN:

251370

Hom.:

AF XY:

0.00764

AC XY:

1038

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.0390

Gnomad NFE exome

AF:

0.00700

Gnomad OTH exome

AF:

0.00635

GnomAD4 exome

AF:

0.00744

AC:

10882

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

5265

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.00725

Gnomad4 OTH exome

AF:

0.00684

GnomAD4 genome

AF:

0.00711

AC:

1081

AN:

151986

Hom.:

Cov.:

AF XY:

0.00883

AC XY:

656

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.000916

Gnomad4 AMR

AF:

0.00460

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.0437

Gnomad4 NFE

AF:

0.00708

Gnomad4 OTH

AF:

0.00665

Alfa

AF:

0.00583

Hom.:

Bravo

AF:

0.00415

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00558

AC:

ExAC

AF:

0.00659

AC:

800

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00682

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0020

DANN

Benign

0.22

DEOGEN2

Benign

0.0075

.;T;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.23

.;T;.;T

MetaRNN

Benign

0.0034

T;T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.010

N;.;.;.

REVEL

Benign

0.017

Sift

Benign

0.74

T;.;.;.

Sift4G

Benign

0.33

T;T;T;.

Vest4

0.060

MutPred

0.23

Loss of glycosylation at T60 (P = 0.0394);.;.;Loss of glycosylation at T60 (P = 0.0394);

MVP

0.13

MPC

0.15

ClinPred

0.0032

GERP RS

-8.8

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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