Variant rs2018417 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000668.6(ADH1B):c.666G>T(p.Ala222=) 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 75 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6 linkuse as main transcript	c.666G>T	p.Ala222=	synonymous_variant	6/9	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2 linkuse as main transcript	c.546G>T	p.Ala182=	synonymous_variant	7/10		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13 linkuse as main transcript	c.666G>T	p.Ala222=	synonymous_variant	6/9	1	NM_000668.6	ENSP00000306606	P1	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

GnomAD3 exomes

AF:

0.0222

AC:

5555

AN:

250462

Hom.:

105

AF XY:

0.0221

AC XY:

2998

AN XY:

135364

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 SAS exome

AF:

0.0157

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

Gnomad4 AFR exome

AF:

0.0352

Gnomad4 AMR exome

AF:

0.00915

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0182

Gnomad4 FIN exome

AF:

0.0359

Gnomad4 NFE exome

AF:

0.0346

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0292

AC:

4451

AN:

152230

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

2122

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0350

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0345

Gnomad4 NFE

AF:

0.0330

Gnomad4 OTH

AF:

0.0241

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.61

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over