dbSNP rs10009145: ADH4:c.980-46C>T (chr4-99126778-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 NM_000670.5(ADH4):c.980-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,534,828 control chromosomes in the GnomAD database, including 146,925 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 0.34 ( 10412 hom., cov: 32)

Exomes 𝑓: 0.44 ( 136513 hom. )

Consequence

ADH4
NM_000670.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0630

Publications

9 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:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000670.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH4	NM_000670.5	MANE Select	c.980-46C>T	intron	N/A	NP_000661.2	P08319-1
ADH4	NM_001306171.2		c.1037-46C>T	intron	N/A	NP_001293100.1	P08319-2
ADH4	NM_001306172.2		c.1037-46C>T	intron	N/A	NP_001293101.1	P08319-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH4	ENST00000265512.12	TSL:1 MANE Select	c.980-46C>T	intron	N/A	ENSP00000265512.7	P08319-1
ENSG00000246090	ENST00000500358.6	TSL:1	n.429-6777G>A	intron	N/A
ADH4	ENST00000505590.5	TSL:5	c.1037-46C>T	intron	N/A	ENSP00000425416.1	P08319-2

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51551

AN:

151956

Hom.:

10409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.352

GnomAD2 exomes

AF:

0.394

AC:

93292

AN:

236856

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.420

Gnomad EAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.470

Gnomad NFE exome

AF:

0.446

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.435

AC:

601934

AN:

1382754

Hom.:

136513

Cov.:

AF XY:

0.438

AC XY:

298457

AN XY:

681126

show subpopulations

African (AFR)

AF:

0.122

AC:

3932

AN:

32276

American (AMR)

AF:

0.329

AC:

13770

AN:

41884

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

9692

AN:

23786

East Asian (EAS)

AF:

0.105

AC:

4099

AN:

38908

South Asian (SAS)

AF:

0.519

AC:

38695

AN:

74618

European-Finnish (FIN)

AF:

0.463

AC:

22746

AN:

49154

Middle Eastern (MID)

AF:

0.443

AC:

2398

AN:

5418

European-Non Finnish (NFE)

AF:

0.455

AC:

482712

AN:

1060052

Other (OTH)

AF:

0.422

AC:

23890

AN:

56658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

16079

32158

48237

64316

80395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14886

29772

44658

59544

74430

<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:

0.339

AC:

51555

AN:

152074

Hom.:

10412

Cov.:

AF XY:

0.342

AC XY:

25437

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.134

AC:

5559

AN:

41506

American (AMR)

AF:

0.330

AC:

5035

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1362

AN:

3470

East Asian (EAS)

AF:

0.117

AC:

607

AN:

5174

South Asian (SAS)

AF:

0.498

AC:

2400

AN:

4824

European-Finnish (FIN)

AF:

0.464

AC:

4893

AN:

10550

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.448

AC:

30457

AN:

67960

Other (OTH)

AF:

0.356

AC:

751

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1609

3218

4827

6436

8045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.394

Hom.:

2443

Bravo

AF:

0.314

Asia WGS

AF:

0.361

AC:

1256

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.64

PhyloP100

-0.063

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over