Genetic Variant ADH1B:c.-149delA (chr4-99321479-CT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000881097.1(ADH1B):c.-149delA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 652,582 control chromosomes in the GnomAD database, including 26 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0051 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 23 hom. )

Consequence

ADH1B
ENST00000881097.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.398

Publications

2 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000881097.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.-149delA		upstream_gene	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.-391delA		upstream_gene	N/A	NP_001273579.1	D6RHZ6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH1B	ENST00000881097.1		c.-149delA	5_prime_UTR	Exon 1 of 9	ENSP00000551156.1
ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.-149delA	upstream_gene	N/A	ENSP00000306606.8	P00325-1
ADH1B	ENST00000625860.2	TSL:1	c.-269delA	upstream_gene	N/A	ENSP00000486614.1	P00325-2

Frequencies

GnomAD3 genomes

AF:

0.00506

AC:

769

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00819

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00801

Gnomad OTH

AF:

0.00623

GnomAD4 exome

AF:

0.00542

AC:

2710

AN:

500370

Hom.:

AF XY:

0.00513

AC XY:

1381

AN XY:

268946

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

13370

American (AMR)

AF:

0.00501

AC:

131

AN:

26158

Ashkenazi Jewish (ASJ)

AF:

0.00580

AC:

AN:

13438

East Asian (EAS)

AF:

0.00

AC:

AN:

28468

South Asian (SAS)

AF:

0.000989

AC:

AN:

48528

European-Finnish (FIN)

AF:

0.000716

AC:

AN:

33500

Middle Eastern (MID)

AF:

0.0117

AC:

AN:

3330

European-Non Finnish (NFE)

AF:

0.00719

AC:

2214

AN:

307812

Other (OTH)

AF:

0.00602

AC:

155

AN:

25766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

124

248

373

497

621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00505

AC:

769

AN:

152212

Hom.:

Cov.:

AF XY:

0.00454

AC XY:

338

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

41548

American (AMR)

AF:

0.00818

AC:

125

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00802

AC:

545

AN:

67992

Other (OTH)

AF:

0.00616

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00491

Hom.:

Bravo

AF:

0.00533

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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4-99321479-CTT-CT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over