4-99412689-C-G

Position:

• chr4-99412689-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.*459G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,378 control chromosomes in the GnomAD database, including 46,285 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 0.78 (46183 hom., cov: 32)
  • Exomes 𝑓: 0.78 (102 hom.)
• Consequence: ADH7 NM_000673.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.*459G>C		3_prime_UTR_variant	9/9	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.*459G>C		3_prime_UTR_variant	9/9		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.*459G>C		3_prime_UTR_variant	9/9	1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.*459G>C		3_prime_UTR_variant	9/9	1		ENSP00000209665

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117813 AN: 151926 Hom.: 46148 Cov.: 32

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.778 AC: 260 AN: 334 Hom.: 102 Cov.: 0 AF XY: 0.766 AC XY: 144 AN XY: 188

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.850

Gnomad4 FIN exome AF: 0.786

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.775 AC: 117900 AN: 152044 Hom.: 46183 Cov.: 32 AF XY: 0.769 AC XY: 57159 AN XY: 74294

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.727

Alfa AF: 0.782 Hom.: 25584

Bravo AF: 0.764

Asia WGS AF: 0.602 AC: 2087 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.79

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: rs894369; hg19: chr4-100333846;