rs11652709

chr17-58193733-G-Cchr17-58193733-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000502.6(EPX):c.366G>C(p.Gln122His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,610,026 control chromosomes in the GnomAD database, including 79,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.29 (6694 hom., cov: 32)
  • Exomes 𝑓: 0.31 (72885 hom.)
• Consequence: EPX NM_000502.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059196055).
• BP6: Variant 17-58193733-G-C is Benign according to our data. Variant chr17-58193733-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPX	NM_000502.6	c.366G>C	p.Gln122His	missense_variant	4/13	ENST00000225371.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPX	ENST00000225371.6	c.366G>C	p.Gln122His	missense_variant	4/13	2	NM_000502.6	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43958 AN: 151978 Hom.: 6684 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.287

GnomAD3 exomes AF: 0.286 AC: 71267 AN: 249256 Hom.: 11025 AF XY: 0.290 AC XY: 39075 AN XY: 134820

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.278

Gnomad EAS exome AF: 0.104

Gnomad SAS exome AF: 0.292

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.310 AC: 452537 AN: 1457930 Hom.: 72885 Cov.: 34 AF XY: 0.310 AC XY: 225005 AN XY: 725280

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.0877

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.289 AC: 44007 AN: 152096 Hom.: 6694 Cov.: 32 AF XY: 0.290 AC XY: 21587 AN XY: 74352

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0905

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.286

Alfa AF: 0.307 Hom.: 5684

Bravo AF: 0.270

TwinsUK AF: 0.324 AC: 1202

ALSPAC AF: 0.317 AC: 1221

ESP6500AA AF: 0.243 AC: 1070

ESP6500EA AF: 0.318 AC: 2731

ExAC AF: 0.286 AC: 34743

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	0.32	P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.29
Sift	Benign	0.12	T
Sift4G	Benign	0.59	T
Polyphen		1.0	D
Vest4		0.18
MutPred		0.32		Loss of disorder (P = 0.0852);
MPC		0.52
ClinPred		0.068	T
GERP RS		3.6
Varity_R		0.14
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs11652709; hg19: chr17-56271094; COSMIC: COSV56596359;