Genetic Variant ENST00000503461.5:n.926T>G (chr4-99282290-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000503461.5(ADH1A):n.926T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 1,613,972 control chromosomes in the GnomAD database, including 9,161 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 0.092 ( 983 hom., cov: 32)

Exomes 𝑓: 0.091 ( 8178 hom. )

Consequence

ADH1A
ENST00000503461.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.251

Publications

11 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=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1A	NM_000667.4 link	c.828+56T>G		intron_variant	Intron 6 of 8	ENST00000209668.3	NP_000658.1	P07327
LOC100507053	NR_037884.1 link	n.3790-4505A>C		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3 link	c.828+56T>G		intron_variant	Intron 6 of 8	1	NM_000667.4	ENSP00000209668.2		P07327

Frequencies

GnomAD3 genomes

AF:

0.0924

AC:

14051

AN:

152140

Hom.:

978

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0556

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.0832

Gnomad EAS

AF:

0.0894

Gnomad SAS

AF:

0.0590

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0805

Gnomad OTH

AF:

0.0917

GnomAD2 exomes

AF:

0.120

AC:

29926

AN:

250290

AF XY:

0.108

show subpopulations

Gnomad AFR exome

AF:

0.0560

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.0876

Gnomad EAS exome

AF:

0.0805

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0847

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0912

AC:

133255

AN:

1461714

Hom.:

8178

Cov.:

AF XY:

0.0889

AC XY:

64654

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0561

AC:

1877

AN:

33472

American (AMR)

AF:

0.343

AC:

15341

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0829

AC:

2167

AN:

26136

East Asian (EAS)

AF:

0.0775

AC:

3076

AN:

39698

South Asian (SAS)

AF:

0.0481

AC:

4153

AN:

86258

European-Finnish (FIN)

AF:

0.126

AC:

6744

AN:

53420

Middle Eastern (MID)

AF:

0.0784

AC:

452

AN:

5768

European-Non Finnish (NFE)

AF:

0.0848

AC:

94324

AN:

1111856

Other (OTH)

AF:

0.0848

AC:

5121

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

6795

13590

20386

27181

33976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3638

7276

10914

14552

18190

<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:

0.0924

AC:

14073

AN:

152258

Hom.:

983

Cov.:

AF XY:

0.0969

AC XY:

7215

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0554

AC:

2303

AN:

41564

American (AMR)

AF:

0.235

AC:

3593

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0832

AC:

289

AN:

3472

East Asian (EAS)

AF:

0.0893

AC:

462

AN:

5176

South Asian (SAS)

AF:

0.0599

AC:

289

AN:

4828

European-Finnish (FIN)

AF:

0.134

AC:

1417

AN:

10596

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0806

AC:

5480

AN:

68020

Other (OTH)

AF:

0.0926

AC:

195

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

619

1239

1858

2478

3097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0880

Hom.:

1777

Bravo

AF:

0.102

Asia WGS

AF:

0.118

AC:

411

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.4

(source)

DANN

Benign

0.56

PhyloP100

-0.25

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over