Variant rs11652709 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6694 hom., cov: 32)

Exomes 𝑓: 0.31 ( 72885 hom. )

Consequence

EPX
NM_000502.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.15

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
EPX	NM_000502.6 link	c.366G>C	p.Gln122His	missense_variant	4/13	ENST00000225371.6	NP_000493.1	P11678

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPX	ENST00000225371.6 link	c.366G>C	p.Gln122His	missense_variant	4/13	2	NM_000502.6	ENSP00000225371.5		P11678

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43958

AN:

151978

Hom.:

6684

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.310

AC XY:

225005

AN XY:

725280

show subpopulations

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.:

AF XY:

0.290

AC XY:

21587

AN XY:

74352

show subpopulations

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

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.1

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.4

REVEL

Benign

0.29

Sift

Benign

0.12

Sift4G

Benign

0.59

Polyphen

1.0

Vest4

0.18

MutPred

0.32

Loss of disorder (P = 0.0852);

MPC

0.52

ClinPred

0.068

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over