17-58280472-G-A

Position:

• chr17-58280472-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000250.2(MPO):​c.155-13C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,668 control chromosomes in the GnomAD database, including 17,658 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 0.11 (1280 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16378 hom.)
• Consequence: MPO NM_000250.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

Genes affected

MPO (HGNC:7218): (myeloperoxidase) Myeloperoxidase (MPO) is a heme protein synthesized during myeloid differentiation that constitutes the major component of neutrophil azurophilic granules. Produced as a single chain precursor, myeloperoxidase is subsequently cleaved into a light and heavy chain. The mature myeloperoxidase is a tetramer composed of 2 light chains and 2 heavy chains. This enzyme produces hypohalous acids central to the microbicidal activity of neutrophils. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPO	NM_000250.2	c.155-13C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000225275.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPO	ENST00000225275.4	c.155-13C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000250.2	P1
MPO	ENST00000580005.1	n.84-13C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17335 AN: 152108 Hom.: 1279 Cov.: 32

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.147

GnomAD3 exomes AF: 0.116 AC: 28913 AN: 249738 Hom.: 2081 AF XY: 0.117 AC XY: 15842 AN XY: 135016

Gnomad AFR exome AF: 0.0336

Gnomad AMR exome AF: 0.0891

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.000164

Gnomad SAS exome AF: 0.0392

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.143 AC: 209038 AN: 1461442 Hom.: 16378 Cov.: 33 AF XY: 0.140 AC XY: 101992 AN XY: 727014

Gnomad4 AFR exome AF: 0.0314

Gnomad4 AMR exome AF: 0.0946

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0404

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.114 AC: 17333 AN: 152226 Hom.: 1280 Cov.: 32 AF XY: 0.112 AC XY: 8308 AN XY: 74414

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0354

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.145

Alfa AF: 0.134 Hom.: 282

Bravo AF: 0.112

Asia WGS AF: 0.0220 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.8
DANN	Benign	0.64

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: rs2856857; hg19: chr17-56357833;