Genetic Variant MPO:c.1365+20G>A (chr17-58275522-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.49

Publications

6 publications found

Variant links:

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]

MPO links:

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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=-0.93).

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 link	c.1365+20G>A		intron_variant	Intron 8 of 11	ENST00000225275.4	NP_000241.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MPO	ENST00000225275.4 link	c.1365+20G>A	intron_variant	Intron 8 of 11	1	NM_000250.2	ENSP00000225275.3
MPO	ENST00000578493.2 link	n.698+20G>A	intron_variant	Intron 3 of 6	3
MPO	ENST00000699291.1 link	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0722

AC XY:

52471

AN XY:

727116

show subpopulations

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:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0746

AC:

82932

AN:

1111868

Other (OTH)

AF:

0.0630

AC:

3805

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

5371

10742

16113

21484

26855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3042

6084

9126

12168

15210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0595

AC:

9049

AN:

152174

Hom.:

388

Cov.:

AF XY:

0.0617

AC XY:

4591

AN XY:

74404

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0766

AC:

5211

AN:

67986

Other (OTH)

AF:

0.0564

AC:

119

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

399

798

1196

1595

1994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0030

(source)

DANN

Benign

0.38

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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