Genetic Variant ENSG00000246090:n.4160+68A>T (chr4-99291016-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000500358.6(ENSG00000246090):n.4160+68A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,277,528 control chromosomes in the GnomAD database, including 39,512 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 ( 6877 hom., cov: 31)

Exomes 𝑓: 0.29 ( 32635 hom. )

Consequence

ENSG00000246090
ENST00000500358.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

10 publications found

Variant links:

Genes affected

ENSG00000246090 (HGNC:):

ENSG00000246090 links:

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:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1 link	n.4160+68A>T		intron_variant	Intron 7 of 9
ADH1A	NM_000667.4 link	c.-102T>A		upstream_gene_variant		ENST00000209668.3	NP_000658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3 link	c.-102T>A		upstream_gene_variant		1	NM_000667.4	ENSP00000209668.2

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41492

AN:

151126

Hom.:

6881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.294

AC:

331578

AN:

1126286

Hom.:

32635

Cov.:

AF XY:

0.292

AC XY:

166820

AN XY:

571770

show subpopulations

African (AFR)

AF:

0.0791

AC:

2112

AN:

26706

American (AMR)

AF:

0.168

AC:

6130

AN:

36500

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

8349

AN:

21568

East Asian (EAS)

AF:

0.0225

AC:

851

AN:

37888

South Asian (SAS)

AF:

0.157

AC:

11541

AN:

73356

European-Finnish (FIN)

AF:

0.310

AC:

15524

AN:

50002

Middle Eastern (MID)

AF:

0.314

AC:

1555

AN:

4956

European-Non Finnish (NFE)

AF:

0.328

AC:

271622

AN:

826878

Other (OTH)

AF:

0.287

AC:

13894

AN:

48432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

8694

17388

26083

34777

43471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8150

16300

24450

32600

40750

<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:

0.274

AC:

41493

AN:

151242

Hom.:

6877

Cov.:

AF XY:

0.267

AC XY:

19727

AN XY:

73856

show subpopulations

African (AFR)

AF:

0.101

AC:

4154

AN:

41324

American (AMR)

AF:

0.264

AC:

4004

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1596

AN:

3456

East Asian (EAS)

AF:

0.0339

AC:

175

AN:

5164

South Asian (SAS)

AF:

0.159

AC:

762

AN:

4802

European-Finnish (FIN)

AF:

0.338

AC:

3506

AN:

10386

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.385

AC:

26078

AN:

67662

Other (OTH)

AF:

0.329

AC:

688

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1351

2702

4054

5405

6756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.156

Hom.:

346

Bravo

AF:

0.262

Asia WGS

AF:

0.0990

AC:

349

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.70

PhyloP100

0.24

PromoterAI

-0.027

Neutral

(source)

Mutation Taster

=300/0

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