Genetic Variant ADH6:c.567+76C>G (chr4-99210006-G-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.567+76C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,440,230 control chromosomes in the GnomAD database, including 231,794 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 0.63 ( 32083 hom., cov: 32)

Exomes 𝑓: 0.55 ( 199711 hom. )

Consequence

ADH6
NM_001102470.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.28

Publications

7 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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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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 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.567+76C>G	intron	N/A	NP_001095940.1	P28332-2
ADH6	NM_000672.4		c.567+76C>G	intron	N/A	NP_000663.1	P28332-1
LOC100507053	NR_037884.1		n.3789+5575G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH6	ENST00000394899.6	TSL:2 MANE Select	c.567+76C>G	intron	N/A	ENSP00000378359.2	P28332-2
ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+5575G>C	intron	N/A
ADH6	ENST00000881183.1		c.588+76C>G	intron	N/A	ENSP00000551242.1

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96273

AN:

151892

Hom.:

32031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.828

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.620

GnomAD4 exome

AF:

0.549

AC:

707872

AN:

1288220

Hom.:

199711

AF XY:

0.549

AC XY:

355471

AN XY:

647340

show subpopulations

African (AFR)

AF:

0.841

AC:

25206

AN:

29966

American (AMR)

AF:

0.607

AC:

26065

AN:

42940

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

14275

AN:

24616

East Asian (EAS)

AF:

0.891

AC:

34487

AN:

38692

South Asian (SAS)

AF:

0.552

AC:

44962

AN:

81386

European-Finnish (FIN)

AF:

0.500

AC:

21720

AN:

43440

Middle Eastern (MID)

AF:

0.545

AC:

2972

AN:

5450

European-Non Finnish (NFE)

AF:

0.525

AC:

507542

AN:

967086

Other (OTH)

AF:

0.561

AC:

30643

AN:

54644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

15580

31159

46739

62318

77898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14042

28084

42126

56168

70210

<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:

0.634

AC:

96380

AN:

152010

Hom.:

32083

Cov.:

AF XY:

0.632

AC XY:

46985

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.829

AC:

34369

AN:

41468

American (AMR)

AF:

0.629

AC:

9595

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2020

AN:

3466

East Asian (EAS)

AF:

0.879

AC:

4540

AN:

5166

South Asian (SAS)

AF:

0.572

AC:

2756

AN:

4820

European-Finnish (FIN)

AF:

0.500

AC:

5280

AN:

10568

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.527

AC:

35826

AN:

67950

Other (OTH)

AF:

0.617

AC:

1303

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1688

3376

5064

6752

8440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.410

Hom.:

975

Bravo

AF:

0.654

Asia WGS

AF:

0.646

AC:

2247

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.28

(source)

DANN

Benign

0.73

PhyloP100

-2.3

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