Genetic Variant ADH1B:p.Lys20Lys (chr4-99318845-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000668.6(ADH1B):c.60A>G(p.Lys20Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,612,808 control chromosomes in the GnomAD database, including 1,439 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 0.042 ( 155 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1284 hom. )

Consequence

ADH1B
NM_000668.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.214

Publications

11 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=-0.214 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6 link	c.60A>G	p.Lys20Lys	synonymous_variant	Exon 2 of 9	ENST00000305046.13	NP_000659.2	P00325-1V9HW50
ADH1B	NM_001286650.2 link	c.-61A>G		5_prime_UTR_variant	Exon 3 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.60A>G	p.Lys20Lys	synonymous_variant	Exon 2 of 9	1	NM_000668.6	ENSP00000306606.8		P00325-1

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6330

AN:

152082

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0446

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0536

Gnomad ASJ

AF:

0.0395

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0545

Gnomad FIN

AF:

0.0607

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0365

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0446

AC:

11216

AN:

251260

AF XY:

0.0429

show subpopulations

Gnomad AFR exome

AF:

0.0439

Gnomad AMR exome

AF:

0.0785

Gnomad ASJ exome

AF:

0.0342

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.0363

Gnomad OTH exome

AF:

0.0482

GnomAD4 exome

AF:

0.0378

AC:

55213

AN:

1460608

Hom.:

1284

Cov.:

AF XY:

0.0380

AC XY:

27597

AN XY:

726650

show subpopulations

African (AFR)

AF:

0.0464

AC:

1549

AN:

33380

American (AMR)

AF:

0.0775

AC:

3464

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0359

AC:

937

AN:

26116

East Asian (EAS)

AF:

0.000126

AC:

AN:

39668

South Asian (SAS)

AF:

0.0522

AC:

4504

AN:

86222

European-Finnish (FIN)

AF:

0.0648

AC:

3461

AN:

53402

Middle Eastern (MID)

AF:

0.0309

AC:

178

AN:

5762

European-Non Finnish (NFE)

AF:

0.0350

AC:

38869

AN:

1111002

Other (OTH)

AF:

0.0372

AC:

2246

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

2677

5354

8031

10708

13385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1484

2968

4452

5936

7420

<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:

0.0416

AC:

6335

AN:

152200

Hom.:

155

Cov.:

AF XY:

0.0423

AC XY:

3145

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0445

AC:

1848

AN:

41526

American (AMR)

AF:

0.0538

AC:

822

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0395

AC:

137

AN:

3468

East Asian (EAS)

AF:

0.000580

AC:

AN:

5170

South Asian (SAS)

AF:

0.0546

AC:

263

AN:

4818

European-Finnish (FIN)

AF:

0.0607

AC:

644

AN:

10606

Middle Eastern (MID)

AF:

0.0308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0365

AC:

2483

AN:

68006

Other (OTH)

AF:

0.0393

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

310

620

930

1240

1550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0361

Hom.:

Bravo

AF:

0.0427

Asia WGS

AF:

0.0380

AC:

132

AN:

3478

EpiCase

AF:

0.0314

EpiControl

AF:

0.0331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.7

(source)

DANN

Benign

0.72

PhyloP100

-0.21

Mutation Taster

=97/3

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