Genetic Variant NM_000250.2: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.

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	P05164-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPO	ENST00000225275.4	TSL:1 MANE Select	c.1365+20G>A	intron	N/A	ENSP00000225275.3	P05164-1
MPO	ENST00000578493.2	TSL:3	n.698+20G>A	intron	N/A
MPO	ENST00000699291.1		n.491-1853G>A	intron	N/A	ENSP00000514272.1	A0A8V8TPE5

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over