Variant rs2298753 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000669.5(ADH1C):c.*2A>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 0.0959 in 1,613,352 control chromosomes in the GnomAD database, including 8,000 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 0.079 ( 579 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7421 hom. )

Consequence

ADH1C
NM_000669.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.493

Variant links:

Genes affected

ADH1C (HGNC:251): (alcohol dehydrogenase 1C (class I), gamma polypeptide) This gene encodes class I alcohol dehydrogenase, gamma subunit, which 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. Class I alcohol dehydrogenase, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation to acetaldehyde, thus playing 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. An association between ADH1C polymorphism and alcohol dependence has not been established. [provided by RefSeq, Sep 2019]

ADH1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1C	NM_000669.5 linkuse as main transcript	c.*2A>G		3_prime_UTR_variant	9/9	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 linkuse as main transcript	n.1157A>G		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6 linkuse as main transcript	c.*2A>G		3_prime_UTR_variant	9/9	1	NM_000669.5	ENSP00000426083	P1

Frequencies

GnomAD3 genomes

AF:

0.0794

AC:

12079

AN:

152100

Hom.:

572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0947

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0602

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0718

GnomAD3 exomes

AF:

0.101

AC:

25338

AN:

251172

Hom.:

1534

AF XY:

0.0995

AC XY:

13512

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.0528

Gnomad EAS exome

AF:

0.0575

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.0981

Gnomad OTH exome

AF:

0.0869

GnomAD4 exome

AF:

0.0976

AC:

142609

AN:

1461134

Hom.:

7421

Cov.:

AF XY:

0.0968

AC XY:

70379

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.0223

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.0537

Gnomad4 EAS exome

AF:

0.0496

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.0984

Gnomad4 OTH exome

AF:

0.0938

GnomAD4 genome

AF:

0.0794

AC:

12087

AN:

152218

Hom.:

579

Cov.:

AF XY:

0.0817

AC XY:

6082

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0269

Gnomad4 AMR

AF:

0.0947

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.0597

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.0767

Alfa

AF:

0.0730

Hom.:

306

Bravo

AF:

0.0741

Asia WGS

AF:

0.107

AC:

370

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

DANN

Benign

0.62

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over