17-58275522-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000250.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPO	NM_000250.2	MANE Select	c.1365+20G>A		intron	N/A	NP_000241.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPO	ENST00000225275.4	TSL:1 MANE Select	c.1365+20G>A		intron	N/A	ENSP00000225275.3
	MPO	ENST00000578493.2	TSL:3	n.698+20G>A		intron	N/A
	MPO	ENST00000699291.1		n.491-1853G>A		intron	N/A	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

GnomAD2 exomes AF: 0.0738 AC: 18534 AN: 251248 AF XY: 0.0715

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 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

African (AFR) AF: 0.00995 AC: 333 AN: 33476

American (AMR) AF: 0.0734 AC: 3281 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0246 AC: 643 AN: 26136

East Asian (EAS) AF: 0.127 AC: 5048 AN: 39692

South Asian (SAS) AF: 0.0531 AC: 4580 AN: 86252

European-Finnish (FIN) AF: 0.122 AC: 6517 AN: 53392

Middle Eastern (MID) AF: 0.0159 AC: 91 AN: 5740

European-Non Finnish (NFE) AF: 0.0746 AC: 82932 AN: 1111868

Other (OTH) AF: 0.0630 AC: 3805 AN: 60386

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

African (AFR) AF: 0.0132 AC: 548 AN: 41542

American (AMR) AF: 0.0484 AC: 740 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.116 AC: 597 AN: 5168

South Asian (SAS) AF: 0.0618 AC: 298 AN: 4822

European-Finnish (FIN) AF: 0.128 AC: 1359 AN: 10578

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5211 AN: 67986

Other (OTH) AF: 0.0564 AC: 119 AN: 2110

Alfa AF: 0.0482 Hom.: 132

Bravo AF: 0.0519

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0030
DANN	Benign	0.38
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11575868; hg19: chr17-56352883; COSMIC: COSV56564442; COSMIC: COSV56564442;