Genetic Variant ADH7:c.18+194G>A (chr4-99435022-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001166504.2(ADH7):c.78+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,534,720 control chromosomes in the GnomAD database, including 83,229 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 6705 hom., cov: 32)

Exomes 𝑓: 0.33 ( 76524 hom. )

Consequence

ADH7
NM_001166504.2 splice_region, intron

Scores

Splicing: ADA: 0.9165

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.243

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH7	NM_000673.7 link	c.18+194G>A		intron_variant	Intron 1 of 8	ENST00000437033.7	NP_000664.3	P40394
ADH7	NM_001166504.2 link	c.78+5G>A		splice_region_variant, 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+194G>A	intron_variant	Intron 1 of 8	1	NM_000673.7	ENSP00000414254.2	A0A0C4DG85
ADH7	ENST00000209665.8 link	c.54+194G>A	intron_variant	Intron 1 of 8	1		ENSP00000209665.4	P40394-1
ADH7	ENST00000476959.5 link	c.78+5G>A	splice_region_variant, intron_variant	Intron 1 of 8	2		ENSP00000420269.1	P40394-2
ADH7	ENST00000482593.5 link	c.-267+194G>A	intron_variant	Intron 1 of 9	3		ENSP00000420613.1	E9PFG0

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43002

AN:

151910

Hom.:

6697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.279

GnomAD3 exomes

AF:

0.328

AC:

48101

AN:

146714

Hom.:

8333

AF XY:

0.322

AC XY:

25146

AN XY:

78078

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.333

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.328

AC:

453812

AN:

1382690

Hom.:

76524

Cov.:

AF XY:

0.327

AC XY:

223043

AN XY:

682660

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.349

Gnomad4 NFE exome

AF:

0.337

Gnomad4 OTH exome

AF:

0.330

GnomAD4 genome

AF:

0.283

AC:

43036

AN:

152030

Hom.:

6705

Cov.:

AF XY:

0.288

AC XY:

21367

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.355

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.323

Hom.:

17020

Bravo

AF:

0.282

Asia WGS

AF:

0.318

AC:

1107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.9

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.92

dbscSNV1_RF

Benign

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over