Genetic Variant ADH1A:c.829-978A>G (chr4-99281257-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000667.4(ADH1A):c.829-978A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,098 control chromosomes in the GnomAD database, including 51,013 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 0.82 ( 51009 hom., cov: 31)

Exomes 𝑓: 0.83 ( 4 hom. )

Consequence

ADH1A
NM_000667.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

7 publications found

Variant links:

Genes affected

ADH1A (HGNC:249): (alcohol dehydrogenase 1A (class I), alpha polypeptide) This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence. [provided by RefSeq, Nov 2010]

ADH1A links:

ENSG00000246090 (HGNC:):

ENSG00000246090 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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000667.4. 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
	ADH1A	NM_000667.4	MANE Select	c.829-978A>G		intron	N/A	NP_000658.1	P07327
	LOC100507053	NR_037884.1		n.3790-5538T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH1A	ENST00000209668.3	TSL:1 MANE Select	c.829-978A>G	intron	N/A	ENSP00000209668.2	P07327
ENSG00000246090	ENST00000500358.6	TSL:1	n.3790-5538T>C	intron	N/A
ADH1A	ENST00000908169.1		c.829-229A>G	intron	N/A	ENSP00000578228.1

Frequencies

GnomAD3 genomes

AF:

0.816

AC:

124034

AN:

151968

Hom.:

50957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.910

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.805

Gnomad ASJ

AF:

0.844

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.699

Gnomad FIN

AF:

0.733

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.774

Gnomad OTH

AF:

0.826

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.800

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.816

AC:

124141

AN:

152086

Hom.:

51009

Cov.:

AF XY:

0.811

AC XY:

60299

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.910

AC:

37777

AN:

41522

American (AMR)

AF:

0.805

AC:

12299

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

2930

AN:

3470

East Asian (EAS)

AF:

0.911

AC:

4696

AN:

5156

South Asian (SAS)

AF:

0.700

AC:

3371

AN:

4816

European-Finnish (FIN)

AF:

0.733

AC:

7735

AN:

10554

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.774

AC:

52632

AN:

67974

Other (OTH)

AF:

0.822

AC:

1735

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1109

2219

3328

4438

5547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.797

Hom.:

8192

Bravo

AF:

0.830

Asia WGS

AF:

0.748

AC:

2599

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.84

(source)

DANN

Benign

0.59

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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