rs11079339

Variant names:

• chr17-58193081-A-G
• rs11079339
• NM_000502.6:c.120A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 26 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 (MetaRNN=0.0022176504).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPX	NM_000502.6	MANE Select	c.120A>G	p.Ile40Met	missense	Exon 2 of 13	NP_000493.1	P11678

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPX	ENST00000225371.6	TSL:2 MANE Select	c.120A>G	p.Ile40Met	missense	Exon 2 of 13	ENSP00000225371.5	P11678

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

GnomAD2 exomes AF: 0.142 AC: 35804 AN: 251460 AF XY: 0.137

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 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

African (AFR) AF: 0.142 AC: 4761 AN: 33456

American (AMR) AF: 0.143 AC: 6390 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 2069 AN: 26130

East Asian (EAS) AF: 0.0931 AC: 3695 AN: 39694

South Asian (SAS) AF: 0.0845 AC: 7285 AN: 86240

European-Finnish (FIN) AF: 0.268 AC: 14321 AN: 53400

Middle Eastern (MID) AF: 0.0554 AC: 319 AN: 5762

European-Non Finnish (NFE) AF: 0.144 AC: 160457 AN: 1110940

Other (OTH) AF: 0.128 AC: 7753 AN: 60354

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

African (AFR) AF: 0.142 AC: 5901 AN: 41516

American (AMR) AF: 0.137 AC: 2104 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3470

East Asian (EAS) AF: 0.0993 AC: 515 AN: 5186

South Asian (SAS) AF: 0.0919 AC: 443 AN: 4820

European-Finnish (FIN) AF: 0.283 AC: 2992 AN: 10574

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10050 AN: 67982

Other (OTH) AF: 0.151 AC: 319 AN: 2112

Alfa AF: 0.141 Hom.: 6530

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 v4.9

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
PhyloP100		-0.55
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
PromoterAI		-0.00020	Neutral
Varity_R		0.082
gMVP		0.50
Mutation Taster		=97/3	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: rs11079339; hg19: chr17-56270442; COSMIC: COSV56596674;