Genetic Variant ADH6:c.829-15A>G (chr4-99207596-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_001102470.2(ADH6):c.829-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,610,410 control chromosomes in the GnomAD database, including 120,390 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 0.43 ( 15308 hom., cov: 32)

Exomes 𝑓: 0.36 ( 105082 hom. )

Consequence

ADH6
NM_001102470.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32

Publications

11 publications found

Variant links:

Genes affected

ADH6 (HGNC:255): (alcohol dehydrogenase 6 (class V)) This gene encodes class V alcohol dehydrogenase, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This gene is expressed in the stomach as well as in the liver, and it contains a glucocorticoid response element upstream of its 5' UTR, which is a steroid hormone receptor binding site. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ADH6 links:

ENSG00000246090 (HGNC:):

ENSG00000246090 links:

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new If you want to explore the variant's impact on the transcript NM_001102470.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102470.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH6	NM_001102470.2	MANE Select	c.829-15A>G	intron	N/A	NP_001095940.1	P28332-2
ADH6	NM_000672.4		c.829-15A>G	intron	N/A	NP_000663.1	P28332-1
LOC100507053	NR_037884.1		n.3789+3165T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH6	ENST00000394899.6	TSL:2 MANE Select	c.829-15A>G	intron	N/A	ENSP00000378359.2	P28332-2
ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+3165T>C	intron	N/A
ADH6	ENST00000881183.1		c.850-15A>G	intron	N/A	ENSP00000551242.1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65154

AN:

151828

Hom.:

15295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.876

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.411

GnomAD2 exomes

AF:

0.427

AC:

106112

AN:

248636

AF XY:

0.419

show subpopulations

Gnomad AFR exome

AF:

0.566

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.886

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.363

AC:

529539

AN:

1458464

Hom.:

105082

Cov.:

AF XY:

0.365

AC XY:

264947

AN XY:

725524

show subpopulations

African (AFR)

AF:

0.568

AC:

18963

AN:

33370

American (AMR)

AF:

0.497

AC:

22044

AN:

44366

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

8827

AN:

26056

East Asian (EAS)

AF:

0.890

AC:

35283

AN:

39648

South Asian (SAS)

AF:

0.443

AC:

38189

AN:

86122

European-Finnish (FIN)

AF:

0.297

AC:

15816

AN:

53320

Middle Eastern (MID)

AF:

0.347

AC:

1996

AN:

5754

European-Non Finnish (NFE)

AF:

0.330

AC:

365639

AN:

1109592

Other (OTH)

AF:

0.378

AC:

22782

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14814

29628

44442

59256

74070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12182

24364

36546

48728

60910

<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:

0.429

AC:

65209

AN:

151946

Hom.:

15308

Cov.:

AF XY:

0.432

AC XY:

32086

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.559

AC:

23175

AN:

41438

American (AMR)

AF:

0.465

AC:

7093

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1204

AN:

3466

East Asian (EAS)

AF:

0.877

AC:

4515

AN:

5150

South Asian (SAS)

AF:

0.480

AC:

2313

AN:

4820

European-Finnish (FIN)

AF:

0.298

AC:

3152

AN:

10564

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22495

AN:

67940

Other (OTH)

AF:

0.410

AC:

864

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1781

3562

5342

7123

8904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.369

Hom.:

18404

Bravo

AF:

0.450

Asia WGS

AF:

0.580

AC:

2013

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.63

(source)

DANN

Benign

0.67

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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