Variant rs1693482 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000669.5(ADH1C):c.815G>A(p.Arg272Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,612,334 control chromosomes in the GnomAD database, including 124,558 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

Frequency

Genomes: 𝑓 0.31 ( 8870 hom., cov: 33)

Exomes 𝑓: 0.39 ( 115688 hom. )

Consequence

ADH1C
NM_000669.5 missense

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: 0.447

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.4730564E-5).

BP6

Variant 4-99342808-C-T is Benign according to our data. Variant chr4-99342808-C-T is described in ClinVar as [protective]. Clinvar id is 18179.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 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.815G>A	p.Arg272Gln	missense_variant	6/9	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 linkuse as main transcript	n.855+31G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6 linkuse as main transcript	c.815G>A	p.Arg272Gln	missense_variant	6/9	1	NM_000669.5	ENSP00000426083	P1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47499

AN:

152058

Hom.:

8863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.0816

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.514

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.279

GnomAD3 exomes

AF:

0.345

AC:

86408

AN:

250778

Hom.:

16724

AF XY:

0.348

AC XY:

47165

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.0777

Gnomad SAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.517

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

AF:

0.388

AC:

565821

AN:

1460158

Hom.:

115688

Cov.:

AF XY:

0.384

AC XY:

279183

AN XY:

726466

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.323

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.0649

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.312

AC:

47519

AN:

152176

Hom.:

8870

Cov.:

AF XY:

0.313

AC XY:

23285

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.272

Gnomad4 EAS

AF:

0.0812

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.514

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.371

Hom.:

7401

Bravo

AF:

0.287

TwinsUK

AF:

0.407

AC:

1511

ALSPAC

AF:

0.397

AC:

1531

ESP6500AA

AF:

0.150

AC:

660

ESP6500EA

AF:

0.384

AC:

3304

ExAC

AF:

0.342

AC:

41574

Asia WGS

AF:

0.220

AC:

762

AN:

3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Alcohol dependence

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jun 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.77

MetaRNN

Benign

0.000065

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.27

Sift4G

Uncertain

0.011

Polyphen

0.0020

Vest4

0.067

GERP RS

1.8

Varity_R

0.078

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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