rs1573496

Positions:

• chr4-99428512-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM1 BP4_Strong BA1

The NM_000673.7(ADH7):​c.239G>C​(p.Gly80Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 1,613,220 control chromosomes in the GnomAD database, including 8,053 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 0.077 (662 hom., cov: 32)
  • Exomes 𝑓: 0.094 (7391 hom.)
• Consequence: ADH7 NM_000673.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

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 -10 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity ADH7_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.002137661).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.239G>C	p.Gly80Ala	missense_variant	3/9	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.299G>C	p.Gly100Ala	missense_variant	3/9		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.239G>C	p.Gly80Ala	missense_variant	3/9	1	NM_000673.7	ENSP00000414254	P1

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11715 AN: 152012 Hom.: 663 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0987

GnomAD3 exomes AF: 0.0855 AC: 21398 AN: 250368 Hom.: 1211 AF XY: 0.0876 AC XY: 11852 AN XY: 135236

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.0570

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0637

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0939 AC: 137267 AN: 1461090 Hom.: 7391 Cov.: 32 AF XY: 0.0938 AC XY: 68160 AN XY: 726762

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.0592

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0635

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.0986

Gnomad4 OTH exome AF: 0.0977

GnomAD4 genome AF: 0.0770 AC: 11714 AN: 152130 Hom.: 662 Cov.: 32 AF XY: 0.0783 AC XY: 5824 AN XY: 74372

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0776

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.106 Hom.: 731

Bravo AF: 0.0707

TwinsUK AF: 0.0949 AC: 352

ALSPAC AF: 0.0929 AC: 358

ESP6500AA AF: 0.0182 AC: 80

ESP6500EA AF: 0.110 AC: 950

ExAC AF: 0.0839 AC: 10184

EpiCase AF: 0.108

EpiControl AF: 0.0999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;.;.;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
MetaRNN	Benign	0.0021	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.;.;.
MutationTaster	Benign	9.9e-7	P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;.
Polyphen		0.97	D;.;.;.;.
Vest4		0.35
MPC		0.049
ClinPred		0.065	T
GERP RS		3.4
Varity_R		0.74
gMVP		0.52

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: rs1573496; hg19: chr4-100349669; COSMIC: COSV52923422;