Variant 4-99344976-T-C 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.453A>G(p.Thr151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,613,916 control chromosomes in the GnomAD database, including 70,561 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 ( 8988 hom., cov: 33)

Exomes 𝑓: 0.26 ( 61573 hom. )

Consequence

ADH1C
NM_000669.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.08

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=-0.96).

BP7

Synonymous conserved (PhyloP=-6.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1C	NM_000669.5 linkuse as main transcript	c.453A>G	p.Thr151=	synonymous_variant	5/9	ENST00000515683.6
ADH1C	NR_133005.2 linkuse as main transcript	n.524A>G		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ADH1C	ENST00000515683.6 linkuse as main transcript	c.453A>G	p.Thr151=	synonymous_variant	5/9	1	NM_000669.5	P1
ADH1C	ENST00000510055.5 linkuse as main transcript	c.333A>G	p.Thr111=	synonymous_variant	6/7	3
ADH1C	ENST00000511397.3 linkuse as main transcript	c.351A>G	p.Thr117=	synonymous_variant	4/5	3
ADH1C	ENST00000505942.2 linkuse as main transcript	n.476A>G		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47308

AN:

151926

Hom.:

8988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.460

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.753

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.297

AC:

74637

AN:

251412

Hom.:

15193

AF XY:

0.306

AC XY:

41564

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.461

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.765

Gnomad SAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.261

AC:

381031

AN:

1461872

Hom.:

61573

Cov.:

AF XY:

0.268

AC XY:

195072

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.192

Gnomad4 EAS exome

AF:

0.823

Gnomad4 SAS exome

AF:

0.503

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.311

AC:

47336

AN:

152044

Hom.:

8988

Cov.:

AF XY:

0.317

AC XY:

23536

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.754

Gnomad4 SAS

AF:

0.534

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.226

Hom.:

1892

Bravo

AF:

0.315

Asia WGS

AF:

0.512

AC:

1783

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.12

DANN

Benign

0.35

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