dbSNP rs1789883: ADH1B:c.567+680C>T (chr4-99315218-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000668.6(ADH1B):c.567+680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 152,518 control chromosomes in the GnomAD database, including 82 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 0.027 ( 82 hom., cov: 33)

Exomes 𝑓: 0.034 ( 0 hom. )

Consequence

ADH1B
NM_000668.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.524

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0274 (4173/152130) while in subpopulation SAS AF = 0.0539 (260/4820). AF 95% confidence interval is 0.0486. There are 82 homozygotes in GnomAd4. There are 2123 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 82 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6 link	c.567+680C>T		intron_variant	Intron 5 of 8	ENST00000305046.13	NP_000659.2	P00325-1V9HW50
ADH1B	NM_001286650.2 link	c.447+680C>T		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+680C>T		intron_variant	Intron 5 of 8	1	NM_000668.6	ENSP00000306606.8		P00325-1

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4169

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00604

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0425

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0539

Gnomad FIN

AF:

0.0555

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0254

GnomAD4 exome

AF:

0.0335

AC:

AN:

388

Hom.:

Cov.:

AF XY:

0.0303

AC XY:

AN XY:

198

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0435

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.100

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0313

AC:

AN:

320

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0274

AC:

4173

AN:

152130

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

2123

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00602

AC:

250

AN:

41510

American (AMR)

AF:

0.0427

AC:

652

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3466

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0539

AC:

260

AN:

4820

European-Finnish (FIN)

AF:

0.0555

AC:

586

AN:

10564

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0325

AC:

2211

AN:

68006

Other (OTH)

AF:

0.0256

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

210

420

630

840

1050

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:

0.0312

Hom.:

118

Bravo

AF:

0.0267

Asia WGS

AF:

0.0320

AC:

110

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.38

(source)

DANN

Benign

0.39

PhyloP100

-0.52

Mutation Taster

=100/0

polymorphism

(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