Variant 4-99310850-T-C 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.1018A>G(p.Lys340Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADH1B
NM_000668.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37

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 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/exons	MANE	UniProt
ADH1B	NM_000668.6 linkuse as main transcript	c.1018A>G	p.Lys340Glu	missense_variant	8/9	ENST00000305046.13
ADH1B	NM_001286650.2 linkuse as main transcript	c.898A>G	p.Lys300Glu	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13 linkuse as main transcript	c.1018A>G	p.Lys340Glu	missense_variant	8/9	1	NM_000668.6	P1	P00325-1
ADH1B	ENST00000625860.2 linkuse as main transcript	c.898A>G	p.Lys300Glu	missense_variant	8/9	1			P00325-2
ADH1B	ENST00000506651.5 linkuse as main transcript	c.898A>G	p.Lys300Glu	missense_variant	9/10	2			P00325-2
ADH1B	ENST00000515694.4 linkuse as main transcript	n.3113A>G		non_coding_transcript_exon_variant	8/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461272

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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

Cov.:

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

Nov 15, 2021

The c.1018A>G (p.K340E) alteration is located in exon 8 (coding exon 8) of the ADH1B gene. This alteration results from a A to G substitution at nucleotide position 1018, causing the lysine (K) at amino acid position 340 to be replaced by a glutamic acid (E). 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

Benign

0.23

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.0065

MetaRNN

Uncertain

0.50

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.7

D;.;.;.

REVEL

Benign

0.22

Sift

Benign

0.11

T;.;.;.

Sift4G

Benign

0.45

T;T;T;.

Vest4

0.41

MutPred

0.45

Loss of methylation at K340 (P = 0.0184);.;.;Loss of methylation at K340 (P = 0.0184);

MVP

0.29

MPC

0.35

ClinPred

0.95

GERP RS

3.7

gMVP

0.68

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over