dbSNP rs10853004: EPX:c.594+44A>G (chr17-58194136-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

eosinophil peroxidase deficiency
Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

EPX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPX	NM_000502.6 link	c.594+44A>G		intron_variant	Intron 5 of 12	ENST00000225371.6	NP_000493.1	P11678

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPX	ENST00000225371.6 link	c.594+44A>G		intron_variant	Intron 5 of 12	2	NM_000502.6	ENSP00000225371.5		P11678

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44038

AN:

151944

Hom.:

6686

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.286

AC:

67741

AN:

236810

AF XY:

0.290

show subpopulations

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 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.:

AF XY:

0.309

AC XY:

223313

AN XY:

721540

show subpopulations

African (AFR)

AF:

0.248

AC:

8282

AN:

33346

American (AMR)

AF:

0.189

AC:

8437

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7341

AN:

26062

East Asian (EAS)

AF:

0.0906

AC:

3591

AN:

39648

South Asian (SAS)

AF:

0.302

AC:

25894

AN:

85852

European-Finnish (FIN)

AF:

0.421

AC:

20939

AN:

49792

Middle Eastern (MID)

AF:

0.226

AC:

1280

AN:

5656

European-Non Finnish (NFE)

AF:

0.322

AC:

355624

AN:

1105010

Other (OTH)

AF:

0.290

AC:

17395

AN:

60062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

16014

32028

48043

64057

80071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.290

AC:

44075

AN:

152062

Hom.:

6695

Cov.:

AF XY:

0.291

AC XY:

21611

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.252

AC:

10442

AN:

41478

American (AMR)

AF:

0.208

AC:

3185

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

968

AN:

3466

East Asian (EAS)

AF:

0.0970

AC:

502

AN:

5174

South Asian (SAS)

AF:

0.286

AC:

1380

AN:

4822

European-Finnish (FIN)

AF:

0.422

AC:

4458

AN:

10560

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22092

AN:

67964

Other (OTH)

AF:

0.291

AC:

615

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1599

3198

4796

6395

7994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.308

Hom.:

4644

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

(source)

DANN

Benign

0.78

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs10853004

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over