rs971074

Positions:

• chr4-99420704-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000673.7(ADH7):​c.654G>A​(p.Arg218=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,613,624 control chromosomes in the GnomAD database, including 11,731 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 0.13 (1435 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10296 hom.)
• Consequence: ADH7 NM_000673.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.672 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH7	NM_000673.7	c.654G>A	p.Arg218=	synonymous_variant	6/9	ENST00000437033.7
ADH7	NM_001166504.2	c.714G>A	p.Arg238=	synonymous_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH7	ENST00000437033.7	c.654G>A	p.Arg218=	synonymous_variant	6/9	1	NM_000673.7	P1
ADH7	ENST00000209665.8	c.690G>A	p.Arg230=	synonymous_variant	6/9	1
ADH7	ENST00000476959.5	c.714G>A	p.Arg238=	synonymous_variant	6/9	2
ADH7	ENST00000482593.5	c.483G>A	p.Arg161=	synonymous_variant	7/10	3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20202 AN: 151930 Hom.: 1430 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.139

GnomAD3 exomes AF: 0.121 AC: 30480 AN: 251046 Hom.: 1986 AF XY: 0.120 AC XY: 16271 AN XY: 135652

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.115 AC: 168798 AN: 1461576 Hom.: 10296 Cov.: 33 AF XY: 0.115 AC XY: 83807 AN XY: 727090

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.133 AC: 20245 AN: 152048 Hom.: 1435 Cov.: 32 AF XY: 0.134 AC XY: 9945 AN XY: 74318

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.140

Alfa AF: 0.123 Hom.: 2812

Bravo AF: 0.134

Asia WGS AF: 0.117 AC: 404 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.1
DANN	Benign	0.65

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: rs971074; hg19: chr4-100341861; COSMIC: COSV52919715; COSMIC: COSV52919715;