Variant chr4-99345173-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000515683.6(ADH1C):c.347+6T>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.38 in 1,611,602 control chromosomes in the GnomAD database, including 124,409 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 ( 8854 hom., cov: 33)

Exomes 𝑓: 0.39 ( 115555 hom. )

Consequence

ADH1C
ENST00000515683.6 splice_donor_region, intron

Scores

Splicing: ADA: 0.9660

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.99

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 -8 ACMG points.

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.347+6T>C		splice_donor_region_variant, intron_variant		ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 linkuse as main transcript	n.418+6T>C		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ADH1C	ENST00000515683.6 linkuse as main transcript	c.347+6T>C	splice_donor_region_variant, intron_variant	1	NM_000669.5	ENSP00000426083	P1
ADH1C	ENST00000510055.5 linkuse as main transcript	c.227+6T>C	splice_donor_region_variant, intron_variant	3		ENSP00000478439
ADH1C	ENST00000511397.3 linkuse as main transcript	c.245+6T>C	splice_donor_region_variant, intron_variant	3		ENSP00000478545
ADH1C	ENST00000505942.2 linkuse as main transcript	n.370+6T>C	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47472

AN:

151998

Hom.:

8848

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:

0.0814

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.279

GnomAD3 exomes

AF:

0.343

AC:

85445

AN:

248982

Hom.:

16307

AF XY:

0.347

AC XY:

46666

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.0774

Gnomad SAS exome

AF:

0.325

Gnomad FIN exome

AF:

0.516

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.388

AC:

565694

AN:

1459486

Hom.:

115555

Cov.:

AF XY:

0.384

AC XY:

279111

AN XY:

725994

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.322

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.0648

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:

0.312

AC:

47493

AN:

152116

Hom.:

8854

Cov.:

AF XY:

0.313

AC XY:

23246

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.272

Gnomad4 EAS

AF:

0.0810

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.513

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.282

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

-0.78

CADD

Benign

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Pathogenic

0.77

SpliceAI score (max)

0.010

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