dbSNP rs4147531: ENSG00000246090:n.4160+92G>A (chr4-99291040-G-A) – 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+92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 949,306 control chromosomes in the GnomAD database, including 88,908 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 0.39 ( 12645 hom., cov: 31)

Exomes 𝑓: 0.42 ( 76263 hom. )

Consequence

ENSG00000246090
ENST00000500358.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

13 publications found

Variant links:

COSMIC-nc: COSV52925045

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:

Genome browser will be placed here

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=-1.02).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1 link	n.4160+92G>A		intron_variant	Intron 7 of 9
ADH1A	NM_000667.4 link	c.-126C>T		upstream_gene_variant		ENST00000209668.3	NP_000658.1	P07327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3 link	c.-126C>T		upstream_gene_variant		1	NM_000667.4	ENSP00000209668.2		P07327

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59174

AN:

151532

Hom.:

12643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

0.419

AC:

334225

AN:

797656

Hom.:

76263

Cov.:

AF XY:

0.412

AC XY:

172722

AN XY:

418848

show subpopulations

African (AFR)

AF:

0.224

AC:

4520

AN:

20190

American (AMR)

AF:

0.543

AC:

19362

AN:

35674

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

10598

AN:

19378

East Asian (EAS)

AF:

0.0956

AC:

3494

AN:

36560

South Asian (SAS)

AF:

0.221

AC:

14176

AN:

64022

European-Finnish (FIN)

AF:

0.481

AC:

23593

AN:

49014

Middle Eastern (MID)

AF:

0.431

AC:

1875

AN:

4354

European-Non Finnish (NFE)

AF:

0.453

AC:

240515

AN:

530372

Other (OTH)

AF:

0.422

AC:

16092

AN:

38092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

8637

17274

25910

34547

43184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4412

8824

13236

17648

22060

<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:

0.390

AC:

59210

AN:

151650

Hom.:

12645

Cov.:

AF XY:

0.387

AC XY:

28647

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.233

AC:

9654

AN:

41392

American (AMR)

AF:

0.511

AC:

7782

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1889

AN:

3468

East Asian (EAS)

AF:

0.115

AC:

594

AN:

5156

South Asian (SAS)

AF:

0.217

AC:

1040

AN:

4798

European-Finnish (FIN)

AF:

0.481

AC:

5032

AN:

10470

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.468

AC:

31719

AN:

67832

Other (OTH)

AF:

0.439

AC:

925

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1669

3338

5006

6675

8344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<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:

0.450

Hom.:

26518

Bravo

AF:

0.390

Asia WGS

AF:

0.226

AC:

790

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.45

(source)

DANN

Benign

0.39

PhyloP100

-1.4

PromoterAI

0.017

Neutral

(source)

Splicing

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