Genetic Variant ADH1B:c.*2673G>T (chr4-99305167-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000668.6(ADH1B):c.*2673G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,158 control chromosomes in the GnomAD database, including 14,824 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 14824 hom., cov: 28)

Failed GnomAD Quality Control

Consequence

ADH1B
NM_000668.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42

Publications

13 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6 link	c.*2673G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000305046.13	NP_000659.2	P00325-1V9HW50
ADH1B	NM_001286650.2 link	c.*2673G>T		3_prime_UTR_variant	Exon 10 of 10		NP_001273579.1	P00325-2D6RHZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13 link	c.*2673G>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000668.6	ENSP00000306606.8		P00325-1
ADH1B	ENST00000625860.2 link	c.*2673G>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000486614.1		P00325-2D6RHZ6

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

65887

AN:

151040

Hom.:

14809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.466

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.436

AC:

65941

AN:

151158

Hom.:

14824

Cov.:

AF XY:

0.432

AC XY:

31899

AN XY:

73790

show subpopulations

African (AFR)

AF:

0.394

AC:

16219

AN:

41196

American (AMR)

AF:

0.526

AC:

7987

AN:

15194

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

1866

AN:

3466

East Asian (EAS)

AF:

0.114

AC:

587

AN:

5152

South Asian (SAS)

AF:

0.211

AC:

1012

AN:

4790

European-Finnish (FIN)

AF:

0.496

AC:

5097

AN:

10282

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.466

AC:

31616

AN:

67794

Other (OTH)

AF:

0.464

AC:

966

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1762

3524

5286

7048

8810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.446

Hom.:

3171

Bravo

AF:

0.441

Asia WGS

AF:

0.233

AC:

810

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.29

(source)

DANN

Benign

0.12

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over