rs11079339

Positions:

• chr17-58193081-A-G

Variant summary

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

The NM_000502.6(EPX):​c.120A>G​(p.Ile40Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,612,874 control chromosomes in the GnomAD database, including 17,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 0.15 (1883 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15828 hom.)
• Consequence: EPX NM_000502.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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=0.0022176504).
• BP6: Variant 17-58193081-A-G is Benign according to our data. Variant chr17-58193081-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPX	NM_000502.6	c.120A>G	p.Ile40Met	missense_variant	2/13	ENST00000225371.6	NP_000493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPX	ENST00000225371.6	c.120A>G	p.Ile40Met	missense_variant	2/13	2	NM_000502.6	ENSP00000225371	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22685 AN: 152056 Hom.: 1879 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.142 AC: 35804 AN: 251460 Hom.: 2882 AF XY: 0.137 AC XY: 18648 AN XY: 135904

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.0761

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.0860

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.142 AC: 207050 AN: 1460698 Hom.: 15828 Cov.: 32 AF XY: 0.140 AC XY: 101423 AN XY: 726738

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.0792

Gnomad4 EAS exome AF: 0.0931

Gnomad4 SAS exome AF: 0.0845

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.149 AC: 22714 AN: 152176 Hom.: 1883 Cov.: 32 AF XY: 0.155 AC XY: 11502 AN XY: 74392

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.0919

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.151

Alfa AF: 0.137 Hom.: 3211

Bravo AF: 0.138

TwinsUK AF: 0.147 AC: 544

ALSPAC AF: 0.134 AC: 515

ESP6500AA AF: 0.141 AC: 623

ESP6500EA AF: 0.141 AC: 1212

ExAC AF: 0.138 AC: 16796

Asia WGS AF: 0.117 AC: 407 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.3
DANN	Benign	0.86
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.048
Sift	Benign	0.36	T
Sift4G	Benign	0.26	T
Polyphen		0.0060	B
Vest4		0.053
MPC		0.12
ClinPred		0.0053	T
GERP RS		-6.1
Varity_R		0.082
gMVP		0.50

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: rs11079339; hg19: chr17-56270442; COSMIC: COSV56596674;