rs3785496

Variant names:

• chr17-58196772-A-G
• rs3785496
• NM_000502.6:c.802-167A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

EPX Gene-Disease associations (from GenCC):

• eosinophil peroxidase deficiency

  Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPX	NM_000502.6	c.802-167A>G		intron_variant	Intron 6 of 12	ENST00000225371.6	NP_000493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPX	ENST00000225371.6	c.802-167A>G		intron_variant	Intron 6 of 12	2	NM_000502.6	ENSP00000225371.5

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

African (AFR) AF: 0.332 AC: 13745 AN: 41446

American (AMR) AF: 0.165 AC: 2529 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3468

East Asian (EAS) AF: 0.0921 AC: 477 AN: 5178

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4816

European-Finnish (FIN) AF: 0.341 AC: 3595 AN: 10544

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16334 AN: 67982

Other (OTH) AF: 0.227 AC: 478 AN: 2110

Alfa AF: 0.244 Hom.: 2440

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3785496; hg19: chr17-56274133; COSMIC: COSV56596143;