17-58193136-A-G

Variant names:

• chr17-58193136-A-G
• rs200112800
• NM_000502.6:c.170+5A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000502.6(EPX):​c.170+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,596,400 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: EPX NM_000502.6 splice_region, intron
• Scores: Splicing: ADA: 0.00008222
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.53

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-58193136-A-G is Benign according to our data. Variant chr17-58193136-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 727637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPX	NM_000502.6	c.170+5A>G		splice_region_variant, intron_variant	Intron 2 of 12	ENST00000225371.6	NP_000493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPX	ENST00000225371.6	c.170+5A>G		splice_region_variant, intron_variant	Intron 2 of 12	2	NM_000502.6	ENSP00000225371.5

Frequencies

GnomAD3 genomes AF: 0.000856 AC: 130 AN: 151830 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00119 AC: 298 AN: 251234 AF XY: 0.00116

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00914

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00121 AC: 1747 AN: 1444454 Hom.: 1 Cov.: 29 AF XY: 0.00119 AC XY: 857 AN XY: 719604

Gnomad4 AFR exome AF: 0.000213 AC: 7 AN: 32848

Gnomad4 AMR exome AF: 0.00107 AC: 48 AN: 44712

Gnomad4 ASJ exome AF: 0.00903 AC: 235 AN: 26038

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39626

Gnomad4 SAS exome AF: 0.000768 AC: 66 AN: 85938

Gnomad4 FIN exome AF: 0.0000937 AC: 5 AN: 53382

Gnomad4 NFE exome AF: 0.00116 AC: 1267 AN: 1096436

Gnomad4 Remaining exome AF: 0.00176 AC: 105 AN: 59750

GnomAD4 genome AF: 0.000849 AC: 129 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.000848 AC XY: 63 AN XY: 74306

Gnomad4 AFR AF: 0.000218 AC: 0.000218309 AN: 0.000218309

Gnomad4 AMR AF: 0.000392 AC: 0.000392054 AN: 0.000392054

Gnomad4 ASJ AF: 0.00806 AC: 0.00806452 AN: 0.00806452

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000621 AC: 0.000621118 AN: 0.000621118

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00116 AC: 0.00116183 AN: 0.00116183

Gnomad4 OTH AF: 0.00142 AC: 0.0014218 AN: 0.0014218

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.000994

EpiCase AF: 0.00158

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EPX: BP4 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	14
DANN	Benign	0.70
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000082
dbscSNV1_RF	Benign	0.012
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: rs200112800; hg19: chr17-56270497;