Genetic Variant ADH1C:c.-61+253G>A (chr4-99353129-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000865215.1(ADH1C):c.-61+253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 161,704 control chromosomes in the GnomAD database, including 9,590 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 ( 8902 hom., cov: 31)

Exomes 𝑓: 0.34 ( 688 hom. )

Consequence

ADH1C
ENST00000865215.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.376

Publications

40 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000865215.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
ADH1C	ENST00000865215.1	c.-61+253G>A	intron	N/A	ENSP00000535274.1
ADH1C	ENST00000865216.1	c.-58+253G>A	intron	N/A	ENSP00000535275.1
ADH1C	ENST00000865217.1	c.-57-397G>A	intron	N/A	ENSP00000535276.1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47643

AN:

151776

Hom.:

8895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.0824

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.344

AC:

3378

AN:

9810

Hom.:

688

AF XY:

0.335

AC XY:

1796

AN XY:

5364

show subpopulations

African (AFR)

AF:

0.0769

AC:

AN:

156

American (AMR)

AF:

0.320

AC:

491

AN:

1532

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

AN:

142

East Asian (EAS)

AF:

0.0502

AC:

AN:

578

South Asian (SAS)

AF:

0.315

AC:

324

AN:

1030

European-Finnish (FIN)

AF:

0.516

AC:

AN:

188

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.391

AC:

2245

AN:

5746

Other (OTH)

AF:

0.332

AC:

140

AN:

422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.314

AC:

47666

AN:

151894

Hom.:

8902

Cov.:

AF XY:

0.315

AC XY:

23348

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.144

AC:

5970

AN:

41422

American (AMR)

AF:

0.293

AC:

4480

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

988

AN:

3466

East Asian (EAS)

AF:

0.0820

AC:

424

AN:

5172

South Asian (SAS)

AF:

0.308

AC:

1479

AN:

4804

European-Finnish (FIN)

AF:

0.515

AC:

5416

AN:

10512

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.413

AC:

28023

AN:

67926

Other (OTH)

AF:

0.289

AC:

610

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1526

3052

4578

6104

7630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.357

Hom.:

36476

Bravo

AF:

0.288

Asia WGS

AF:

0.222

AC:

770

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.7

(source)

DANN

Benign

0.67

PhyloP100

-0.38

PromoterAI

-0.036

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over