dbSNP rs11499823: ADH1C:c.-271T>C (chr4-99353592-A-G) – 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.-271T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 152,168 control chromosomes in the GnomAD database, including 576 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 0.079 ( 576 hom., cov: 32)

Consequence

ADH1C
ENST00000865215.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

9 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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new If you want to explore the variant's impact on the transcript ENST00000865215.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.93).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0989 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.-271T>C	5_prime_UTR	Exon 1 of 10	ENSP00000535274.1
ADH1C	ENST00000865216.1	c.-268T>C	5_prime_UTR	Exon 1 of 10	ENSP00000535275.1
ADH1C	ENST00000865217.1	c.-100T>C	5_prime_UTR	Exon 1 of 10	ENSP00000535276.1

Frequencies

GnomAD3 genomes

AF:

0.0794

AC:

12077

AN:

152050

Hom.:

570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0941

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0603

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0718

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0794

AC:

12084

AN:

152168

Hom.:

576

Cov.:

AF XY:

0.0818

AC XY:

6083

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0269

AC:

1119

AN:

41532

American (AMR)

AF:

0.0941

AC:

1439

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

171

AN:

3468

East Asian (EAS)

AF:

0.0598

AC:

310

AN:

5180

South Asian (SAS)

AF:

0.101

AC:

487

AN:

4818

European-Finnish (FIN)

AF:

0.142

AC:

1500

AN:

10578

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6857

AN:

67986

Other (OTH)

AF:

0.0762

AC:

161

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

566

1132

1699

2265

2831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0884

Hom.:

866

Bravo

AF:

0.0740

Asia WGS

AF:

0.106

AC:

367

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.2

(source)

DANN

Benign

0.48

PhyloP100

0.24

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over