rs3785496

Positions:

• chr17-58196772-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000502.6(EPX):​c.802-167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,034 control chromosomes in the GnomAD database, including 5,310 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 0.26 (5310 hom., cov: 32)
• Consequence: EPX NM_000502.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

EPX (HGNC:3423): (eosinophil peroxidase) This gene is a member of the peroxidase gene family and is expressed in eosinophils. The encoded preproprotein is proteolytically processed into covalently attached heavy and light chains to form the mature enzyme, which functions as an oxidant. The enzyme is released at sites of parasitic infection or allergen stimulation to mediate lysis of protozoa or parasitic worms. The gene is found in a gene cluster with other peroxidase genes on chromosome 17. Mutations in this gene result in eosinophil peroxidase deficiency. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPX	NM_000502.6	c.802-167A>G		intron_variant		ENST00000225371.6	NP_000493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPX	ENST00000225371.6	c.802-167A>G		intron_variant		2	NM_000502.6	ENSP00000225371	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39070 AN: 151914 Hom.: 5298 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0919

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.257 AC: 39114 AN: 152034 Hom.: 5310 Cov.: 32 AF XY: 0.258 AC XY: 19206 AN XY: 74300

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0921

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.227

Alfa AF: 0.247 Hom.: 2244

Bravo AF: 0.245

Asia WGS AF: 0.175 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3785496; hg19: chr17-56274133; COSMIC: COSV56596143;