chr4-99428512-C-G

Variant names:

• chr4-99428512-C-G
• rs1573496
• NM_000673.7:c.239G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. 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. 12/21 in silico tools predict 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
• Publications: 56 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000673.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	NM_000673.7	MANE Select	c.239G>C	p.Gly80Ala	missense	Exon 3 of 9	NP_000664.3	A0A0C4DG85
	ADH7	NM_001166504.2		c.299G>C	p.Gly100Ala	missense	Exon 3 of 9	NP_001159976.1	P40394-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	ENST00000437033.7	TSL:1 MANE Select	c.239G>C	p.Gly80Ala	missense	Exon 3 of 9	ENSP00000414254.2	A0A0C4DG85
	ADH7	ENST00000209665.8	TSL:1	c.275G>C	p.Gly92Ala	missense	Exon 3 of 9	ENSP00000209665.4	P40394-1
	ADH7	ENST00000476959.5	TSL:2	c.299G>C	p.Gly100Ala	missense	Exon 3 of 9	ENSP00000420269.1	P40394-2

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

GnomAD2 exomes AF: 0.0855 AC: 21398 AN: 250368 AF XY: 0.0876

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 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

African (AFR) AF: 0.0184 AC: 615 AN: 33460

American (AMR) AF: 0.0592 AC: 2644 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 5246 AN: 26092

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39680

South Asian (SAS) AF: 0.0635 AC: 5471 AN: 86090

European-Finnish (FIN) AF: 0.130 AC: 6940 AN: 53366

Middle Eastern (MID) AF: 0.149 AC: 862 AN: 5766

European-Non Finnish (NFE) AF: 0.0986 AC: 109582 AN: 1111636

Other (OTH) AF: 0.0977 AC: 5895 AN: 60364

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

African (AFR) AF: 0.0171 AC: 710 AN: 41530

American (AMR) AF: 0.0776 AC: 1184 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 671 AN: 3472

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.0500 AC: 241 AN: 4822

European-Finnish (FIN) AF: 0.129 AC: 1367 AN: 10572

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7151 AN: 68000

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

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 v4.9

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
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.8
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	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
Mutation Taster		=83/17	polymorphism (auto)

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

Other links and lift over

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