Variant chr4-99307860-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BA1

The NM_000668.6(ADH1B):c.1108C>T(p.Arg370Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,613,550 control chromosomes in the GnomAD database, including 1,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

Frequency

Genomes: 𝑓 0.054 ( 756 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 705 hom. )

Consequence

ADH1B
NM_000668.6 missense

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: 3.37

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 -11 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity ADH1B_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0020994842).

BP6

Variant 4-99307860-G-A is Benign according to our data. Variant chr4-99307860-G-A is described in ClinVar as [protective]. Clinvar id is 18183.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6 linkuse as main transcript	c.1108C>T	p.Arg370Cys	missense_variant	9/9	ENST00000305046.13
ADH1B	NM_001286650.2 linkuse as main transcript	c.988C>T	p.Arg330Cys	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13 linkuse as main transcript	c.1108C>T	p.Arg370Cys	missense_variant	9/9	1	NM_000668.6	P1	P00325-1
ADH1B	ENST00000625860.2 linkuse as main transcript	c.988C>T	p.Arg330Cys	missense_variant	9/9	1			P00325-2
ADH1B	ENST00000506651.5 linkuse as main transcript	c.988C>T	p.Arg330Cys	missense_variant	10/10	2			P00325-2
ADH1B	ENST00000515694.4 linkuse as main transcript	n.3203C>T		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.0545

AC:

8277

AN:

151978

Hom.:

757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.0393

GnomAD3 exomes

AF:

0.0150

AC:

3780

AN:

251340

Hom.:

306

AF XY:

0.0116

AC XY:

1579

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.00885

Gnomad ASJ exome

AF:

0.00823

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00638

AC:

9326

AN:

1461454

Hom.:

705

Cov.:

AF XY:

0.00566

AC XY:

4116

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.00953

Gnomad4 ASJ exome

AF:

0.00742

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.0545

AC:

8286

AN:

152096

Hom.:

756

Cov.:

AF XY:

0.0529

AC XY:

3936

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.0389

Alfa

AF:

0.0136

Hom.:

254

Bravo

AF:

0.0624

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.187

AC:

824

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0182

AC:

2205

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00302

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Alcohol dependence

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jan 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;T;.

Eigen

Uncertain

0.45

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

.;D;.;D

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.1e-12

P;P

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-6.9

D;.;.;.

REVEL

Benign

0.19

Sift

Uncertain

0.0030

D;.;.;.

Sift4G

Uncertain

0.017

D;D;D;.

Vest4

0.32

MPC

0.83

ClinPred

0.10

GERP RS

3.1

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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