Variant chr4-99339632-T-C 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.1048A>G(p.Ile350Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,609,470 control chromosomes in the GnomAD database, including 124,425 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 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 ( 8849 hom., cov: 31)

Exomes 𝑓: 0.39 ( 115576 hom. )

Consequence

ADH1C
NM_000669.5 missense

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: 3.58

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.5579672E-4).

BP6

Variant 4-99339632-T-C is Benign according to our data. Variant chr4-99339632-T-C is described in ClinVar as [protective]. Clinvar id is 18180.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.1048A>G	p.Ile350Val	missense_variant	8/9	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 linkuse as main transcript	n.1075A>G		non_coding_transcript_exon_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6 linkuse as main transcript	c.1048A>G	p.Ile350Val	missense_variant	8/9	1	NM_000669.5	ENSP00000426083	P1

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47433

AN:

151572

Hom.:

8842

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.0820

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.346

AC:

85871

AN:

248348

Hom.:

16651

AF XY:

0.349

AC XY:

46935

AN XY:

134554

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.0781

Gnomad SAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

AF:

0.388

AC:

565349

AN:

1457778

Hom.:

115576

Cov.:

AF XY:

0.385

AC XY:

278988

AN XY:

725162

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.321

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.0649

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.313

AC:

47454

AN:

151692

Hom.:

8849

Cov.:

AF XY:

0.314

AC XY:

23229

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.272

Gnomad4 EAS

AF:

0.0816

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.366

Hom.:

21518

Bravo

AF:

0.287

TwinsUK

AF:

0.410

AC:

1521

ALSPAC

AF:

0.398

AC:

1532

ESP6500AA

AF:

0.152

AC:

659

ESP6500EA

AF:

0.386

AC:

3319

ExAC

AF:

0.343

AC:

41620

Asia WGS

AF:

0.221

AC:

765

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

0.067

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.0078

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.14

MetaRNN

Benign

0.00046

MutationAssessor

Benign

-1.8

PrimateAI

Benign

0.33

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.014

GERP RS

3.9

Varity_R

0.024

gMVP

0.40

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