Variant 4-99345000-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000669.5(ADH1C):c.429C>T(p.Gly143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,614,148 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

ADH1C
NM_000669.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.642

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 4-99345000-G-A is Benign according to our data. Variant chr4-99345000-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 716191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.642 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1C	NM_000669.5 linkuse as main transcript	c.429C>T	p.Gly143=	synonymous_variant	5/9	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 linkuse as main transcript	n.500C>T		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.429C>T	p.Gly143=	synonymous_variant	5/9	1	NM_000669.5	ENSP00000426083	P1
ADH1C	ENST00000510055.5 linkuse as main transcript	c.309C>T	p.Gly103=	synonymous_variant	6/7	3		ENSP00000478439
ADH1C	ENST00000511397.3 linkuse as main transcript	c.327C>T	p.Gly109=	synonymous_variant	4/5	3		ENSP00000478545
ADH1C	ENST00000505942.2 linkuse as main transcript	n.452C>T		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

269

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00256

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00186

AC:

468

AN:

251370

Hom.:

AF XY:

0.00175

AC XY:

238

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.00642

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00196

AC:

2859

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1371

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000858

Gnomad4 FIN exome

AF:

0.00723

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00177

AC:

269

AN:

152264

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.00256

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00129

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	ADH1C: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 07, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.8

DANN

Benign

0.43

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