4-99420704-C-T

Variant names:

• chr4-99420704-C-T
• rs971074
• NM_000673.7:c.654G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000673.7(ADH7):​c.654G>A​(p.Arg218Arg) 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
• Publications: 70 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 -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 rank	MANE	Protein	UniProt
ADH7	NM_000673.7	c.654G>A	p.Arg218Arg	synonymous_variant	Exon 6 of 9	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.714G>A	p.Arg238Arg	synonymous_variant	Exon 6 of 9		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.654G>A	p.Arg218Arg	synonymous_variant	Exon 6 of 9	1	NM_000673.7	ENSP00000414254.2
ADH7	ENST00000209665.8	c.690G>A	p.Arg230Arg	synonymous_variant	Exon 6 of 9	1		ENSP00000209665.4
ADH7	ENST00000476959.5	c.714G>A	p.Arg238Arg	synonymous_variant	Exon 6 of 9	2		ENSP00000420269.1
ADH7	ENST00000482593.5	c.483G>A	p.Arg161Arg	synonymous_variant	Exon 7 of 10	3		ENSP00000420613.1

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

GnomAD2 exomes AF: 0.121 AC: 30480 AN: 251046 AF XY: 0.120

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 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

African (AFR) AF: 0.173 AC: 5789 AN: 33456

American (AMR) AF: 0.103 AC: 4614 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5615 AN: 26128

East Asian (EAS) AF: 0.119 AC: 4711 AN: 39696

South Asian (SAS) AF: 0.106 AC: 9167 AN: 86258

European-Finnish (FIN) AF: 0.144 AC: 7665 AN: 53410

Middle Eastern (MID) AF: 0.165 AC: 951 AN: 5766

European-Non Finnish (NFE) AF: 0.110 AC: 122653 AN: 1111812

Other (OTH) AF: 0.126 AC: 7633 AN: 60390

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

African (AFR) AF: 0.160 AC: 6629 AN: 41462

American (AMR) AF: 0.124 AC: 1898 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3466

East Asian (EAS) AF: 0.114 AC: 588 AN: 5176

South Asian (SAS) AF: 0.102 AC: 493 AN: 4820

European-Finnish (FIN) AF: 0.141 AC: 1490 AN: 10576

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7926 AN: 67972

Other (OTH) AF: 0.140 AC: 297 AN: 2114

Alfa AF: 0.123 Hom.: 5705

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
PhyloP100		0.67
Mutation Taster		=100/0	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: rs971074; hg19: chr4-100341861; COSMIC: COSV52919715; COSMIC: COSV52919715;