17-58193136-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000502.6(EPX):c.170+5A>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,596,400 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: EPX NM_000502.6 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 0.00008222
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-58193136-A-G is Benign according to our data. Variant chr17-58193136-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 727637.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPX	NM_000502.6	c.170+5A>G		splice_donor_5th_base_variant, intron_variant		ENST00000225371.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPX	ENST00000225371.6	c.170+5A>G		splice_donor_5th_base_variant, intron_variant		2	NM_000502.6	P1

Frequencies

GnomAD3 genomes AF: 0.000856 AC: 130 AN: 151830 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00119 AC: 298 AN: 251234 Hom.: 0 AF XY: 0.00116 AC XY: 157 AN XY: 135884

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00914

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00121 AC: 1747 AN: 1444454 Hom.: 1 Cov.: 29 AF XY: 0.00119 AC XY: 857 AN XY: 719604

Gnomad4 AFR exome AF: 0.000213

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00903

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000768

Gnomad4 FIN exome AF: 0.0000937

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.000849 AC: 129 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.000848 AC XY: 63 AN XY: 74306

Gnomad4 AFR AF: 0.000218

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.000994

EpiCase AF: 0.00158

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	14
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000082
dbscSNV1_RF	Benign	0.012
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: rs200112800; hg19: chr17-56270497;