rs284779

Positions:

• chr4-99417104-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000673.7(ADH7):​c.962-1488G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,906 control chromosomes in the GnomAD database, including 26,494 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 0.57 (26494 hom., cov: 31)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH7	NM_000673.7	c.962-1488G>C		intron_variant		ENST00000437033.7
ADH7	NM_001166504.2	c.1022-1488G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH7	ENST00000437033.7	c.962-1488G>C		intron_variant		1	NM_000673.7	P1
ADH7	ENST00000209665.8	c.998-1488G>C		intron_variant		1
ADH7	ENST00000476959.5	c.1022-1488G>C		intron_variant		2
ADH7	ENST00000482593.5	c.791-1488G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85926 AN: 151788 Hom.: 26451 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.566 AC: 86028 AN: 151906 Hom.: 26494 Cov.: 31 AF XY: 0.561 AC XY: 41645 AN XY: 74210

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.577

Alfa AF: 0.524 Hom.: 2800

Bravo AF: 0.587

Asia WGS AF: 0.506 AC: 1756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.46
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs284779; hg19: chr4-100338261;