17-58275522-C-T

Variant names:

• chr17-58275522-C-T
• rs11575868
• NM_000250.2:c.1365+20G>A

Variant summary

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

The NM_000250.2(MPO):​c.1365+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 1,613,828 control chromosomes in the GnomAD database, including 4,859 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 0.059 (388 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4471 hom.)
• Consequence: MPO NM_000250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPO	NM_000250.2	c.1365+20G>A		intron_variant	Intron 8 of 11	ENST00000225275.4	NP_000241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4	c.1365+20G>A		intron_variant	Intron 8 of 11	1	NM_000250.2	ENSP00000225275.3
MPO	ENST00000578493.2	n.698+20G>A		intron_variant	Intron 3 of 6	3
MPO	ENST00000699291.1	n.491-1853G>A		intron_variant	Intron 2 of 5			ENSP00000514272.1

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9032 AN: 152056 Hom.: 385 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0551

GnomAD3 exomes AF: 0.0738 AC: 18534 AN: 251248 Hom.: 879 AF XY: 0.0715 AC XY: 9715 AN XY: 135810

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.0765

Gnomad ASJ exome AF: 0.0239

Gnomad EAS exome AF: 0.124

Gnomad SAS exome AF: 0.0532

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0744

Gnomad OTH exome AF: 0.0610

GnomAD4 exome AF: 0.0734 AC: 107230 AN: 1461654 Hom.: 4471 Cov.: 32 AF XY: 0.0722 AC XY: 52471 AN XY: 727116

Gnomad4 AFR exome AF: 0.00995

Gnomad4 AMR exome AF: 0.0734

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.0531

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.0746

Gnomad4 OTH exome AF: 0.0630

GnomAD4 genome AF: 0.0595 AC: 9049 AN: 152174 Hom.: 388 Cov.: 32 AF XY: 0.0617 AC XY: 4591 AN XY: 74404

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0618

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.0564

Alfa AF: 0.0472 Hom.: 61

Bravo AF: 0.0519

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0030
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11575868; hg19: chr17-56352883; COSMIC: COSV56564442; COSMIC: COSV56564442;