dbSNP rs283413: ADH1C:p.Gly78* (chr4-99347033-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000669.5(ADH1C):c.232G>T(p.Gly78*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0124 in 1,614,018 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.010 ( 16 hom., cov: 32)

Exomes 𝑓: 0.013 ( 310 hom. )

Consequence

ADH1C
NM_000669.5 stop_gained

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 7.18

Publications

46 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1C	NM_000669.5 link	c.232G>T	p.Gly78*	stop_gained	Exon 3 of 9	ENST00000515683.6	NP_000660.1	P00326
ADH1C	NR_133005.2 link	n.303G>T		non_coding_transcript_exon_variant	Exon 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADH1C	ENST00000515683.6 link	c.232G>T	p.Gly78*	stop_gained	Exon 3 of 9	1	NM_000669.5	ENSP00000426083.1	P00326
ADH1C	ENST00000510055.5 link	c.112G>T	p.Gly38*	stop_gained	Exon 4 of 7	3		ENSP00000478439.1	A0A087WU81
ADH1C	ENST00000511397.3 link	c.130G>T	p.Gly44*	stop_gained	Exon 2 of 5	3		ENSP00000478545.1	A0A087WUC4
ADH1C	ENST00000505942.2 link	n.301G>T		non_coding_transcript_exon_variant	Exon 3 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1573

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0316

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0249

GnomAD4 exome

AF:

0.0126

AC:

18384

AN:

1461800

Hom.:

310

Cov.:

AF XY:

0.0138

AC XY:

10056

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

33480

American (AMR)

AF:

0.0140

AC:

624

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0609

AC:

1590

AN:

26122

East Asian (EAS)

AF:

0.000353

AC:

AN:

39690

South Asian (SAS)

AF:

0.0390

AC:

3362

AN:

86252

European-Finnish (FIN)

AF:

0.00142

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0742

AC:

428

AN:

5766

European-Non Finnish (NFE)

AF:

0.00992

AC:

11036

AN:

1111968

Other (OTH)

AF:

0.0199

AC:

1199

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1071

2142

3212

4283

5354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

428

856

1284

1712

2140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0104

AC:

1576

AN:

152218

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

778

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

41554

American (AMR)

AF:

0.0159

AC:

243

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0674

AC:

234

AN:

3470

East Asian (EAS)

AF:

0.000580

AC:

AN:

5172

South Asian (SAS)

AF:

0.0320

AC:

154

AN:

4812

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

766

AN:

68002

Other (OTH)

AF:

0.0246

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.0105

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Parkinson disease, mitochondrial

Other:1

Jan 01, 2005

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Pathogenic

(source)

PhyloP100

7.2

Vest4

0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over