Genetic Variant ADH1B:c.*531A>G (chr4-99307309-T-C) – 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.*531A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 155,136 control chromosomes in the GnomAD database, including 6,284 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 0.25 ( 6167 hom., cov: 32)

Exomes 𝑓: 0.23 ( 117 hom. )

Consequence

ADH1B
NM_000668.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0240

Publications

68 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6 link	c.*531A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2 link	c.*531A>G		3_prime_UTR_variant	Exon 10 of 10		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ADH1B	ENST00000305046.13 link	c.*531A>G	3_prime_UTR_variant	Exon 9 of 9	1	NM_000668.6	ENSP00000306606.8
ADH1B	ENST00000625860.2 link	c.*531A>G	3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000486614.1
ADH1B	ENST00000515694.4 link	n.3754A>G	non_coding_transcript_exon_variant	Exon 9 of 9	2
ADH1B	ENST00000506651.5 link	c.*531A>G	downstream_gene_variant		2		ENSP00000425998.2

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37856

AN:

152060

Hom.:

6176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.257

GnomAD4 exome

AF:

0.235

AC:

695

AN:

2958

Hom.:

117

Cov.:

AF XY:

0.253

AC XY:

364

AN XY:

1438

show subpopulations

African (AFR)

AF:

0.0769

AC:

AN:

American (AMR)

AF:

0.226

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.374

AC:

AN:

182

European-Finnish (FIN)

AF:

0.201

AC:

AN:

144

Middle Eastern (MID)

AF:

0.313

AC:

AN:

European-Non Finnish (NFE)

AF:

0.227

AC:

504

AN:

2224

Other (OTH)

AF:

0.212

AC:

AN:

222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.249

AC:

37836

AN:

152178

Hom.:

6167

Cov.:

AF XY:

0.252

AC XY:

18731

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.101

AC:

4217

AN:

41552

American (AMR)

AF:

0.201

AC:

3078

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

869

AN:

3464

East Asian (EAS)

AF:

0.799

AC:

4138

AN:

5176

South Asian (SAS)

AF:

0.483

AC:

2327

AN:

4818

European-Finnish (FIN)

AF:

0.215

AC:

2271

AN:

10584

Middle Eastern (MID)

AF:

0.274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.294

AC:

19977

AN:

67984

Other (OTH)

AF:

0.255

AC:

540

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1325

2650

3975

5300

6625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.291

Hom.:

22750

Bravo

AF:

0.238

Asia WGS

AF:

0.476

AC:

1651

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.6

(source)

DANN

Benign

0.58

PhyloP100

0.024

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