Genetic Variant ADH7:c.18+361C>T (chr4-99434855-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_000673.7(ADH7):c.18+361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,146 control chromosomes in the GnomAD database, including 468 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 0.056 ( 468 hom., cov: 32)

Consequence

ADH7
NM_000673.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

2 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH7	NM_000673.7 link	c.18+361C>T		intron_variant	Intron 1 of 8	ENST00000437033.7	NP_000664.3	P40394
ADH7	NM_001166504.2 link	c.78+172C>T		intron_variant	Intron 1 of 8		NP_001159976.1	P40394-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADH7	ENST00000437033.7 link	c.18+361C>T	intron_variant	Intron 1 of 8	1	NM_000673.7	ENSP00000414254.2	A0A0C4DG85
ADH7	ENST00000209665.8 link	c.54+361C>T	intron_variant	Intron 1 of 8	1		ENSP00000209665.4	P40394-1
ADH7	ENST00000476959.5 link	c.78+172C>T	intron_variant	Intron 1 of 8	2		ENSP00000420269.1	P40394-2
ADH7	ENST00000482593.5 link	c.-267+361C>T	intron_variant	Intron 1 of 9	3		ENSP00000420613.1	E9PFG0

Frequencies

GnomAD3 genomes

AF:

0.0554

AC:

8419

AN:

152028

Hom.:

466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0442

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0526

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.0368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0555

AC:

8447

AN:

152146

Hom.:

468

Cov.:

AF XY:

0.0548

AC XY:

4076

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.137

AC:

5682

AN:

41480

American (AMR)

AF:

0.0442

AC:

674

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00950

AC:

AN:

3472

East Asian (EAS)

AF:

0.119

AC:

615

AN:

5178

South Asian (SAS)

AF:

0.0527

AC:

254

AN:

4824

European-Finnish (FIN)

AF:

0.0119

AC:

126

AN:

10602

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0138

AC:

941

AN:

68008

Other (OTH)

AF:

0.0392

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

381

762

1144

1525

1906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0233

Hom.:

202

Bravo

AF:

0.0617

Asia WGS

AF:

0.0880

AC:

305

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.0

(source)

DANN

Benign

0.55

PhyloP100

-0.086

PromoterAI

-0.014

Neutral

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over