dbSNP rs3857224: ADH6:c.828+140G>A (chr4-99208528-C-T) – 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.828+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 919,136 control chromosomes in the GnomAD database, including 73,068 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 0.42 ( 14934 hom., cov: 32)

Exomes 𝑓: 0.36 ( 58134 hom. )

Consequence

ADH6
NM_001102470.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00900

Publications

13 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:

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ADH6	NM_001102470.2 link	c.828+140G>A	intron_variant	Intron 6 of 8	ENST00000394899.6	NP_001095940.1
ADH6	NM_000672.4 link	c.828+140G>A	intron_variant	Intron 6 of 7		NP_000663.1
LOC100507053	NR_037884.1 link	n.3789+4097C>T	intron_variant	Intron 4 of 9
ADH6	NR_132990.2 link	n.563+140G>A	intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH6	ENST00000394899.6 link	c.828+140G>A		intron_variant	Intron 6 of 8	2	NM_001102470.2	ENSP00000378359.2

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64037

AN:

151748

Hom.:

14918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.877

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.404

GnomAD4 exome

AF:

0.364

AC:

279555

AN:

767270

Hom.:

58134

Cov.:

AF XY:

0.367

AC XY:

143636

AN XY:

391236

show subpopulations

African (AFR)

AF:

0.564

AC:

10335

AN:

18320

American (AMR)

AF:

0.477

AC:

10339

AN:

21672

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

5311

AN:

15730

East Asian (EAS)

AF:

0.891

AC:

31051

AN:

34860

South Asian (SAS)

AF:

0.443

AC:

22254

AN:

50248

European-Finnish (FIN)

AF:

0.286

AC:

12465

AN:

43514

Middle Eastern (MID)

AF:

0.351

AC:

968

AN:

2760

European-Non Finnish (NFE)

AF:

0.319

AC:

173334

AN:

543772

Other (OTH)

AF:

0.371

AC:

13498

AN:

36394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8020

16041

24061

32082

40102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4474

8948

13422

17896

22370

<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:

0.422

AC:

64094

AN:

151866

Hom.:

14934

Cov.:

AF XY:

0.425

AC XY:

31539

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.558

AC:

23127

AN:

41414

American (AMR)

AF:

0.458

AC:

6977

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1201

AN:

3468

East Asian (EAS)

AF:

0.877

AC:

4541

AN:

5178

South Asian (SAS)

AF:

0.480

AC:

2312

AN:

4820

European-Finnish (FIN)

AF:

0.284

AC:

2985

AN:

10522

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21717

AN:

67930

Other (OTH)

AF:

0.403

AC:

848

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1767

3533

5300

7066

8833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.366

Hom.:

34069

Bravo

AF:

0.443

Asia WGS

AF:

0.579

AC:

2011

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.1

(source)

DANN

Benign

0.68

PhyloP100

0.0090

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over