dbSNP rs4148886: ADH4:c.18+707A>G (chr4-99143498-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_000670.5(ADH4):c.18+707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 285,438 control chromosomes in the GnomAD database, including 22,087 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 0.36 ( 12034 hom., cov: 32)

Exomes 𝑓: 0.34 ( 10053 hom. )

Consequence

ADH4
NM_000670.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

Publications

7 publications found

Variant links:

Genes affected

ADH4 (HGNC:252): (alcohol dehydrogenase 4 (class II), pi polypeptide) This gene encodes class II alcohol dehydrogenase 4 pi subunit, which is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]

ADH4 links:

ENSG00000246090 (HGNC:):

ENSG00000246090 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ADH4	NM_000670.5 link	c.18+707A>G	intron_variant	Intron 1 of 8	ENST00000265512.12	NP_000661.2	P08319-1V9HVX7
ADH4	NM_001306171.2 link	c.-65-193A>G	intron_variant	Intron 1 of 9		NP_001293100.1	P08319-2V9HVX7
ADH4	NM_001306172.2 link	c.-65-193A>G	intron_variant	Intron 1 of 9		NP_001293101.1	P08319-2V9HVX7
LOC100507053	NR_037884.1 link	n.679+9693T>C	intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12 link	c.18+707A>G		intron_variant	Intron 1 of 8	1	NM_000670.5	ENSP00000265512.7		P08319-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55102

AN:

151840

Hom.:

12016

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.335

GnomAD4 exome

AF:

0.338

AC:

45162

AN:

133480

Hom.:

10053

AF XY:

0.340

AC XY:

23850

AN XY:

70250

show subpopulations

African (AFR)

AF:

0.564

AC:

2720

AN:

4824

American (AMR)

AF:

0.433

AC:

2811

AN:

6498

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

1232

AN:

4280

East Asian (EAS)

AF:

0.900

AC:

9714

AN:

10788

South Asian (SAS)

AF:

0.370

AC:

3712

AN:

10036

European-Finnish (FIN)

AF:

0.250

AC:

1457

AN:

5820

Middle Eastern (MID)

AF:

0.337

AC:

186

AN:

552

European-Non Finnish (NFE)

AF:

0.250

AC:

20730

AN:

82790

Other (OTH)

AF:

0.329

AC:

2600

AN:

7892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

1231

2462

3694

4925

6156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.363

AC:

55168

AN:

151958

Hom.:

12034

Cov.:

AF XY:

0.368

AC XY:

27335

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.535

AC:

22158

AN:

41442

American (AMR)

AF:

0.399

AC:

6087

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

958

AN:

3466

East Asian (EAS)

AF:

0.875

AC:

4527

AN:

5176

South Asian (SAS)

AF:

0.362

AC:

1744

AN:

4818

European-Finnish (FIN)

AF:

0.246

AC:

2589

AN:

10536

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.237

AC:

16094

AN:

67946

Other (OTH)

AF:

0.334

AC:

704

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1619

3237

4856

6474

8093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.279

Hom.:

1372

Bravo

AF:

0.387

Asia WGS

AF:

0.529

AC:

1818

AN:

3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.9

(source)

DANN

Benign

0.87

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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