rs17537595

chr4-99435309-A-Gchr4-99435309-A-T

Variant summary

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

The NM_000673.7(ADH7):c.-76T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,597,230 control chromosomes in the GnomAD database, including 13,866 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 0.10 (1063 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12803 hom.)
• Consequence: ADH7 NM_000673.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH7	NM_000673.7	c.-76T>C		5_prime_UTR_variant	1/9	ENST00000437033.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH7	ENST00000437033.7	c.-76T>C		5_prime_UTR_variant	1/9	1	NM_000673.7	P1
ADH7	ENST00000209665.8	c.-40T>C		5_prime_UTR_variant	1/9	1
ADH7	ENST00000482593.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15956 AN: 152092 Hom.: 1064 Cov.: 32

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0827

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.124 AC: 29384 AN: 236710 Hom.: 2070 AF XY: 0.131 AC XY: 16748 AN XY: 127592

Gnomad AFR exome AF: 0.0377

Gnomad AMR exome AF: 0.0747

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0875

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.129 AC: 186685 AN: 1445020 Hom.: 12803 Cov.: 28 AF XY: 0.131 AC XY: 94420 AN XY: 718722

Gnomad4 AFR exome AF: 0.0387

Gnomad4 AMR exome AF: 0.0739

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0473

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.105 AC: 15947 AN: 152210 Hom.: 1063 Cov.: 32 AF XY: 0.107 AC XY: 7943 AN XY: 74424

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.0865

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0829

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.0997

Alfa AF: 0.125 Hom.: 2662

Bravo AF: 0.0916

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.7
Dann	Benign	0.74

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: rs17537595; hg19: chr4-100356466; COSMIC: COSV52920208; COSMIC: COSV52920208;