Variant chr4-99344955-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000669.5(ADH1C):c.474G>A(p.Val158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,613,934 control chromosomes in the GnomAD database, including 124,699 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 0.31 ( 8857 hom., cov: 32)

Exomes 𝑓: 0.39 ( 115842 hom. )

Consequence

ADH1C
NM_000669.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.860

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 (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=-0.86 with no splicing effect.

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.474G>A	p.Val158=	synonymous_variant	5/9	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 linkuse as main transcript	n.545G>A		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADH1C	ENST00000515683.6 linkuse as main transcript	c.474G>A	p.Val158=	synonymous_variant	5/9	1	NM_000669.5	ENSP00000426083	P1
ADH1C	ENST00000510055.5 linkuse as main transcript	c.354G>A	p.Val118=	synonymous_variant	6/7	3		ENSP00000478439
ADH1C	ENST00000511397.3 linkuse as main transcript	c.372G>A	p.Val124=	synonymous_variant	4/5	3		ENSP00000478545
ADH1C	ENST00000505942.2 linkuse as main transcript	n.497G>A		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47467

AN:

151956

Hom.:

8851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.0813

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.345

AC:

86817

AN:

251430

Hom.:

16799

AF XY:

0.349

AC XY:

47401

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.265

Gnomad EAS exome

AF:

0.0781

Gnomad SAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.517

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

AF:

0.388

AC:

567064

AN:

1461860

Hom.:

115842

Cov.:

AF XY:

0.385

AC XY:

279839

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.323

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:

0.414

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.312

AC:

47488

AN:

152074

Hom.:

8857

Cov.:

AF XY:

0.313

AC XY:

23247

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.272

Gnomad4 EAS

AF:

0.0809

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.513

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.361

Hom.:

4671

Bravo

AF:

0.287

Asia WGS

AF:

0.220

AC:

764

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

1.8

DANN

Benign

0.50

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