rs10853004

Variant names:

• chr17-58194136-A-G
• rs10853004
• NM_000502.6:c.594+44A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-58194136-A-G
• chr17-58194136-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000502.6(EPX):​c.594+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,602,022 control chromosomes in the GnomAD database, including 78,811 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 0.29 (6695 hom., cov: 32)
  • Exomes 𝑓: 0.31 (72116 hom.)
• Consequence: EPX NM_000502.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000502.6. 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
	EPX	NM_000502.6	MANE Select	c.594+44A>G		intron	N/A	NP_000493.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPX	ENST00000225371.6	TSL:2 MANE Select	c.594+44A>G		intron	N/A	ENSP00000225371.5

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44038 AN: 151944 Hom.: 6686 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.286 AC: 67741 AN: 236810 AF XY: 0.290

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.278

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.310 AC: 448783 AN: 1449960 Hom.: 72116 Cov.: 30 AF XY: 0.309 AC XY: 223313 AN XY: 721540

African (AFR) AF: 0.248 AC: 8282 AN: 33346

American (AMR) AF: 0.189 AC: 8437 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7341 AN: 26062

East Asian (EAS) AF: 0.0906 AC: 3591 AN: 39648

South Asian (SAS) AF: 0.302 AC: 25894 AN: 85852

European-Finnish (FIN) AF: 0.421 AC: 20939 AN: 49792

Middle Eastern (MID) AF: 0.226 AC: 1280 AN: 5656

European-Non Finnish (NFE) AF: 0.322 AC: 355624 AN: 1105010

Other (OTH) AF: 0.290 AC: 17395 AN: 60062

GnomAD4 genome AF: 0.290 AC: 44075 AN: 152062 Hom.: 6695 Cov.: 32 AF XY: 0.291 AC XY: 21611 AN XY: 74332

African (AFR) AF: 0.252 AC: 10442 AN: 41478

American (AMR) AF: 0.208 AC: 3185 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3466

East Asian (EAS) AF: 0.0970 AC: 502 AN: 5174

South Asian (SAS) AF: 0.286 AC: 1380 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4458 AN: 10560

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22092 AN: 67964

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.308 Hom.: 4644

Bravo AF: 0.270

Asia WGS AF: 0.204 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.78
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs10853004; hg19: chr17-56271497;