dbSNP rs283411: ADH1C:c.567+62G>T (chr4-99344800-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000669.5(ADH1C):c.567+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 1,588,928 control chromosomes in the GnomAD database, including 3,490 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 0.066 ( 368 hom., cov: 33)

Exomes 𝑓: 0.063 ( 3122 hom. )

Consequence

ADH1C
NM_000669.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.654

Publications

8 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 -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 = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1C	NM_000669.5 link	c.567+62G>T		intron_variant	Intron 5 of 8	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 link	n.638+62G>T		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ADH1C	ENST00000515683.6 link	c.567+62G>T	intron_variant	Intron 5 of 8	1	NM_000669.5	ENSP00000426083.1
ADH1C	ENST00000510055.5 link	c.447+62G>T	intron_variant	Intron 6 of 6	3		ENSP00000478439.1
ADH1C	ENST00000511397.3 link	c.465+62G>T	intron_variant	Intron 4 of 4	3		ENSP00000478545.1
ADH1C	ENST00000505942.2 link	n.*88G>T	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0659

AC:

10027

AN:

152122

Hom.:

366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0609

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.0629

Gnomad ASJ

AF:

0.0942

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0192

Gnomad FIN

AF:

0.0994

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0692

Gnomad OTH

AF:

0.0747

GnomAD4 exome

AF:

0.0631

AC:

90596

AN:

1436688

Hom.:

3122

AF XY:

0.0623

AC XY:

44452

AN XY:

713692

show subpopulations

African (AFR)

AF:

0.0583

AC:

1903

AN:

32618

American (AMR)

AF:

0.0419

AC:

1769

AN:

42250

Ashkenazi Jewish (ASJ)

AF:

0.0993

AC:

2547

AN:

25640

East Asian (EAS)

AF:

0.000101

AC:

AN:

39428

South Asian (SAS)

AF:

0.0237

AC:

2000

AN:

84556

European-Finnish (FIN)

AF:

0.0944

AC:

5016

AN:

53140

Middle Eastern (MID)

AF:

0.0735

AC:

416

AN:

5662

European-Non Finnish (NFE)

AF:

0.0669

AC:

73178

AN:

1094030

Other (OTH)

AF:

0.0634

AC:

3763

AN:

59364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

4255

8510

12766

17021

21276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2636

5272

7908

10544

13180

<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:

0.0659

AC:

10039

AN:

152240

Hom.:

368

Cov.:

AF XY:

0.0644

AC XY:

4795

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0610

AC:

2533

AN:

41542

American (AMR)

AF:

0.0628

AC:

961

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0942

AC:

327

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0190

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0994

AC:

1052

AN:

10586

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0692

AC:

4709

AN:

68014

Other (OTH)

AF:

0.0735

AC:

155

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

486

971

1457

1942

2428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0572

Hom.:

440

Bravo

AF:

0.0657

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.2

(source)

DANN

Benign

0.72

PhyloP100

-0.65

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over