Genetic Variant ADH7:c.260-135A>G (chr4-99428309-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_000673.7(ADH7):c.260-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,219,384 control chromosomes in the GnomAD database, including 4,000 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 0.015 ( 419 hom., cov: 32)

Exomes 𝑓: 0.017 ( 3581 hom. )

Consequence

ADH7
NM_000673.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.742

Publications

4 publications found

Variant links:

Genes affected

ADH7 (HGNC:256): (alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide) This gene encodes class IV alcohol dehydrogenase 7 mu or sigma subunit, 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. The enzyme encoded by this gene is inefficient in ethanol oxidation, but is the most active as a retinol dehydrogenase; thus it may participate in the synthesis of retinoic acid, a hormone important for cellular differentiation. The expression of this gene is much more abundant in stomach than liver, thus differing from the other known gene family members. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ADH7 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH7	NM_000673.7 link	c.260-135A>G		intron_variant	Intron 3 of 8	ENST00000437033.7	NP_000664.3	P40394
ADH7	NM_001166504.2 link	c.320-135A>G		intron_variant	Intron 3 of 8		NP_001159976.1	P40394-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7 link	c.260-135A>G		intron_variant	Intron 3 of 8	1	NM_000673.7	ENSP00000414254.2		A0A0C4DG85

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2289

AN:

152192

Hom.:

420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.396

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00173

Gnomad OTH

AF:

0.00621

GnomAD4 exome

AF:

0.0167

AC:

17770

AN:

1067074

Hom.:

3581

AF XY:

0.0162

AC XY:

8712

AN XY:

536384

show subpopulations

African (AFR)

AF:

0.000459

AC:

AN:

23944

American (AMR)

AF:

0.00123

AC:

AN:

28532

Ashkenazi Jewish (ASJ)

AF:

0.00540

AC:

106

AN:

19614

East Asian (EAS)

AF:

0.442

AC:

15700

AN:

35538

South Asian (SAS)

AF:

0.00297

AC:

189

AN:

63588

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

44598

Middle Eastern (MID)

AF:

0.00176

AC:

AN:

4546

European-Non Finnish (NFE)

AF:

0.00142

AC:

1135

AN:

800162

Other (OTH)

AF:

0.0125

AC:

581

AN:

46552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

581

1162

1744

2325

2906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<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:

0.0150

AC:

2284

AN:

152310

Hom.:

419

Cov.:

AF XY:

0.0175

AC XY:

1304

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41596

American (AMR)

AF:

0.00216

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3470

East Asian (EAS)

AF:

0.396

AC:

2048

AN:

5170

South Asian (SAS)

AF:

0.00518

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00173

AC:

118

AN:

68014

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

135

203

270

338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.00676

Hom.:

424

Bravo

AF:

0.0184

Asia WGS

AF:

0.0980

AC:

340

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.81

(source)

DANN

Benign

0.70

PhyloP100

-0.74

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