rs10853004

chr17-58194136-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.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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPX	NM_000502.6	c.594+44A>G		intron_variant		ENST00000225371.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPX	ENST00000225371.6	c.594+44A>G		intron_variant		2	NM_000502.6	P1

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

GnomAD3 exomes AF: 0.286 AC: 67741 AN: 236810 Hom.: 10466 AF XY: 0.290 AC XY: 37509 AN XY: 129186

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 SAS exome AF: 0.297

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

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.0906

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.290

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

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0970

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.291

Alfa AF: 0.309 Hom.: 4279

Bravo AF: 0.270

Asia WGS AF: 0.204 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.6
Dann	Benign	0.78

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: rs10853004; hg19: chr17-56271497;