Genetic Variant ADH1B:c.567+293G>A (chr4-99315605-C-T) – 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.567+293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 457,870 control chromosomes in the GnomAD database, including 152,756 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 0.81 ( 49742 hom., cov: 32)

Exomes 𝑓: 0.82 ( 103014 hom. )

Consequence

ADH1B
NM_000668.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0800

Publications

24 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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6 link	c.567+293G>A		intron_variant	Intron 5 of 8	ENST00000305046.13	NP_000659.2	P00325-1V9HW50
ADH1B	NM_001286650.2 link	c.447+293G>A		intron_variant	Intron 6 of 9		NP_001273579.1	P00325-2D6RHZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13 link	c.567+293G>A		intron_variant	Intron 5 of 8	1	NM_000668.6	ENSP00000306606.8		P00325-1

Frequencies

GnomAD3 genomes

AF:

0.808

AC:

122869

AN:

152042

Hom.:

49698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.768

Gnomad AMI

AF:

0.927

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.844

Gnomad EAS

AF:

0.913

Gnomad SAS

AF:

0.762

Gnomad FIN

AF:

0.798

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.825

Gnomad OTH

AF:

0.824

GnomAD4 exome

AF:

0.819

AC:

250387

AN:

305710

Hom.:

103014

Cov.:

AF XY:

0.815

AC XY:

132985

AN XY:

163178

show subpopulations

African (AFR)

AF:

0.768

AC:

6924

AN:

9016

American (AMR)

AF:

0.799

AC:

10031

AN:

12554

Ashkenazi Jewish (ASJ)

AF:

0.847

AC:

7666

AN:

9056

East Asian (EAS)

AF:

0.921

AC:

16244

AN:

17634

South Asian (SAS)

AF:

0.751

AC:

30405

AN:

40466

European-Finnish (FIN)

AF:

0.813

AC:

12914

AN:

15886

Middle Eastern (MID)

AF:

0.808

AC:

1054

AN:

1304

European-Non Finnish (NFE)

AF:

0.827

AC:

151180

AN:

182762

Other (OTH)

AF:

0.820

AC:

13969

AN:

17032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2252

4504

6755

9007

11259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

668

1336

2004

2672

3340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.808

AC:

122966

AN:

152160

Hom.:

49742

Cov.:

AF XY:

0.805

AC XY:

59909

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.769

AC:

31888

AN:

41484

American (AMR)

AF:

0.811

AC:

12403

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

2932

AN:

3472

East Asian (EAS)

AF:

0.913

AC:

4727

AN:

5176

South Asian (SAS)

AF:

0.762

AC:

3676

AN:

4822

European-Finnish (FIN)

AF:

0.798

AC:

8437

AN:

10574

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.825

AC:

56091

AN:

68020

Other (OTH)

AF:

0.820

AC:

1732

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1223

2445

3668

4890

6113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.827

Hom.:

47802

Bravo

AF:

0.810

Asia WGS

AF:

0.766

AC:

2662

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

4.8

(source)

DANN

Benign

0.67

PhyloP100

0.080

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over