NM_000673.7:c.-76T>C

Variant names:

• chr4-99435309-A-G
• rs17537595
• NM_000673.7:c.-76T>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.-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
• Publications: 9 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 (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 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.-76T>C		5_prime_UTR	Exon 1 of 9	NP_000664.3	A0A0C4DG85
	ADH7	NM_001166504.2		c.-205T>C		upstream_gene	N/A	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.-76T>C		5_prime_UTR	Exon 1 of 9	ENSP00000414254.2	A0A0C4DG85
	ADH7	ENST00000209665.8	TSL:1	c.-40T>C		5_prime_UTR	Exon 1 of 9	ENSP00000209665.4	P40394-1
	ADH7	ENST00000476959.5	TSL:2	c.-205T>C		upstream_gene	N/A	ENSP00000420269.1	P40394-2

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

GnomAD2 exomes AF: 0.124 AC: 29384 AN: 236710 AF XY: 0.131

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 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

African (AFR) AF: 0.0387 AC: 1281 AN: 33114

American (AMR) AF: 0.0739 AC: 3248 AN: 43926

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3231 AN: 25848

East Asian (EAS) AF: 0.0473 AC: 1859 AN: 39312

South Asian (SAS) AF: 0.162 AC: 13724 AN: 84634

European-Finnish (FIN) AF: 0.173 AC: 9179 AN: 52970

Middle Eastern (MID) AF: 0.155 AC: 889 AN: 5736

European-Non Finnish (NFE) AF: 0.133 AC: 145821 AN: 1099744

Other (OTH) AF: 0.125 AC: 7453 AN: 59736

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

African (AFR) AF: 0.0388 AC: 1611 AN: 41544

American (AMR) AF: 0.0865 AC: 1321 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.0829 AC: 429 AN: 5176

South Asian (SAS) AF: 0.150 AC: 723 AN: 4828

European-Finnish (FIN) AF: 0.173 AC: 1834 AN: 10596

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9242 AN: 68000

Other (OTH) AF: 0.0997 AC: 211 AN: 2116

Alfa AF: 0.120 Hom.: 4101

Bravo AF: 0.0916

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		-0.50
PromoterAI		0.029	Neutral
Mutation Taster		=300/0	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: rs17537595; hg19: chr4-100356466; COSMIC: COSV52920208; COSMIC: COSV52920208;