rs2018417

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000668.6(ADH1B):c.666G>T(p.Ala222Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,613,964 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 75 hom., cov: 32)

Exomes 𝑓: 0.031 ( 833 hom. )

Consequence

ADH1B
NM_000668.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.70

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 4-99313983-C-A is Benign according to our data. Variant chr4-99313983-C-A is described in ClinVar as Benign. ClinVar VariationId is 769290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0292 (4451/152230) while in subpopulation AFR AF = 0.035 (1454/41538). AF 95% confidence interval is 0.0335. There are 75 homozygotes in GnomAd4. There are 2122 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 75 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6 link	c.666G>T	p.Ala222Ala	synonymous_variant	Exon 6 of 9	ENST00000305046.13	NP_000659.2	P00325-1V9HW50
ADH1B	NM_001286650.2 link	c.546G>T	p.Ala182Ala	synonymous_variant	Exon 7 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.666G>T	p.Ala222Ala	synonymous_variant	Exon 6 of 9	1	NM_000668.6	ENSP00000306606.8		P00325-1

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4442

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0349

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0330

Gnomad OTH

AF:

0.0244

GnomAD2 exomes

AF:

0.0222

AC:

5555

AN:

250462

AF XY:

0.0221

show subpopulations

Gnomad AFR exome

AF:

0.0322

Gnomad AMR exome

AF:

0.00825

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0338

Gnomad NFE exome

AF:

0.0293

Gnomad OTH exome

AF:

0.0193

GnomAD4 exome

AF:

0.0312

AC:

45613

AN:

1461734

Hom.:

833

Cov.:

AF XY:

0.0305

AC XY:

22203

AN XY:

727170

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0352

AC:

1177

AN:

33474

American (AMR)

AF:

0.00915

AC:

409

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0146

AC:

382

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0182

AC:

1567

AN:

86246

European-Finnish (FIN)

AF:

0.0359

AC:

1919

AN:

53420

Middle Eastern (MID)

AF:

0.0283

AC:

163

AN:

5766

European-Non Finnish (NFE)

AF:

0.0346

AC:

38507

AN:

1111886

Other (OTH)

AF:

0.0246

AC:

1487

AN:

60390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.389

Heterozygous variant carriers

2306

4612

6919

9225

11531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1462

2924

4386

5848

7310

<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:

0.0292

AC:

4451

AN:

152230

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

2122

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0350

AC:

1454

AN:

41538

American (AMR)

AF:

0.0146

AC:

223

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.0133

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0345

AC:

365

AN:

10590

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0330

AC:

2247

AN:

68024

Other (OTH)

AF:

0.0241

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

216

432

649

865

1081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0232

Hom.:

Bravo

AF:

0.0279

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.61

(source)

DANN

Benign

0.56

PhyloP100

-2.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over