chr4-99419365-C-G

Position:

• chr4-99419365-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.826-244G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,972 control chromosomes in the GnomAD database, including 22,040 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 0.53 (22040 hom., cov: 32)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.826-244G>C		intron_variant		ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.886-244G>C		intron_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.826-244G>C		intron_variant		1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.862-244G>C		intron_variant		1		ENSP00000209665
ADH7	ENST00000476959.5	c.886-244G>C		intron_variant		2		ENSP00000420269
ADH7	ENST00000482593.5	c.655-244G>C		intron_variant		3		ENSP00000420613

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80479 AN: 151854 Hom.: 22015 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.530 AC: 80563 AN: 151972 Hom.: 22040 Cov.: 32 AF XY: 0.535 AC XY: 39769 AN XY: 74272

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.529

Alfa AF: 0.438 Hom.: 1314

Bravo AF: 0.521

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.6
DANN	Benign	0.70

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: rs1154458; hg19: chr4-100340522;