rs17529530

Variant names:

• chr4-99434333-T-A
• rs17529530
• NM_000673.7:c.18+883A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000673.7(ADH7):​c.18+883A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,244 control chromosomes in the GnomAD database, including 82 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 0.024 (82 hom., cov: 32)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 1 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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0237 (3613/152244) while in subpopulation NFE AF = 0.0367 (2498/68014). AF 95% confidence interval is 0.0355. There are 82 homozygotes in GnomAd4. There are 1774 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 82 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	NM_000673.7	MANE Select	c.18+883A>T		intron	N/A	NP_000664.3
	ADH7	NM_001166504.2		c.78+694A>T		intron	N/A	NP_001159976.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	ENST00000437033.7	TSL:1 MANE Select	c.18+883A>T		intron	N/A	ENSP00000414254.2
	ADH7	ENST00000209665.8	TSL:1	c.54+883A>T		intron	N/A	ENSP00000209665.4
	ADH7	ENST00000476959.5	TSL:2	c.78+694A>T		intron	N/A	ENSP00000420269.1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3610 AN: 152126 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.00596

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0237 AC: 3613 AN: 152244 Hom.: 82 Cov.: 32 AF XY: 0.0238 AC XY: 1774 AN XY: 74420

African (AFR) AF: 0.00594 AC: 247 AN: 41556

American (AMR) AF: 0.0128 AC: 195 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0244 AC: 118 AN: 4828

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10602

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0367 AC: 2498 AN: 68014

Other (OTH) AF: 0.0237 AC: 50 AN: 2110

Alfa AF: 0.0323 Hom.: 19

Bravo AF: 0.0218

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.091
DANN	Benign	0.65
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

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: rs17529530; hg19: chr4-100355490;