Genetic Variant ADH1A:c.1103+74G>A (chr4-99279352-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 NM_000667.4(ADH1A):c.1103+74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,506,158 control chromosomes in the GnomAD database, including 60,893 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 0.27 ( 6344 hom., cov: 32)

Exomes 𝑓: 0.26 ( 54549 hom. )

Consequence

ADH1A
NM_000667.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.436

Publications

19 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 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.1103+74G>A		intron	N/A	NP_000658.1	P07327
	LOC100507053	NR_037884.1		n.3790-7443C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH1A	ENST00000209668.3	TSL:1 MANE Select	c.1103+74G>A	intron	N/A	ENSP00000209668.2	P07327
ENSG00000246090	ENST00000500358.6	TSL:1	n.3790-7443C>T	intron	N/A
ADH1A	ENST00000908169.1		c.1136+74G>A	intron	N/A	ENSP00000578228.1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40852

AN:

151856

Hom.:

6350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.261

AC:

353290

AN:

1354184

Hom.:

54549

AF XY:

0.266

AC XY:

177405

AN XY:

667532

show subpopulations

African (AFR)

AF:

0.280

AC:

8087

AN:

28856

American (AMR)

AF:

0.143

AC:

3882

AN:

27178

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

4879

AN:

20326

East Asian (EAS)

AF:

0.818

AC:

30595

AN:

37382

South Asian (SAS)

AF:

0.419

AC:

27788

AN:

66244

European-Finnish (FIN)

AF:

0.165

AC:

8098

AN:

49102

Middle Eastern (MID)

AF:

0.244

AC:

1286

AN:

5266

European-Non Finnish (NFE)

AF:

0.238

AC:

253422

AN:

1064188

Other (OTH)

AF:

0.274

AC:

15253

AN:

55642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

12106

24211

36317

48422

60528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9102

18204

27306

36408

45510

<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:

0.269

AC:

40842

AN:

151974

Hom.:

6344

Cov.:

AF XY:

0.270

AC XY:

20064

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.280

AC:

11590

AN:

41432

American (AMR)

AF:

0.200

AC:

3056

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

862

AN:

3464

East Asian (EAS)

AF:

0.794

AC:

4113

AN:

5178

South Asian (SAS)

AF:

0.441

AC:

2118

AN:

4806

European-Finnish (FIN)

AF:

0.162

AC:

1716

AN:

10574

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16496

AN:

67954

Other (OTH)

AF:

0.260

AC:

549

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1431

2862

4292

5723

7154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.258

Hom.:

8025

Bravo

AF:

0.270

Asia WGS

AF:

0.470

AC:

1632

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

(source)

DANN

Benign

0.33

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over