rs17529530

Positions:

• chr4-99434333-T-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 82 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.18+883A>T		intron_variant		ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.78+694A>T		intron_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.18+883A>T		intron_variant		1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.54+883A>T		intron_variant		1		ENSP00000209665
ADH7	ENST00000476959.5	c.78+694A>T		intron_variant		2		ENSP00000420269
ADH7	ENST00000482593.5	c.-267+883A>T		intron_variant		3		ENSP00000420613

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

Gnomad4 AFR AF: 0.00594

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0244

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0367

Gnomad4 OTH AF: 0.0237

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.091
DANN	Benign	0.65

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: rs17529530; hg19: chr4-100355490;