Genetic Variant MPO:c.1365+86G>A (chr17-58275456-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+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,547,894 control chromosomes in the GnomAD database, including 252 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 0.023 ( 144 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 108 hom. )

Consequence

MPO
NM_000250.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.153

Publications

1 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPO	NM_000250.2 link	c.1365+86G>A		intron_variant	Intron 8 of 11	ENST00000225275.4	NP_000241.1	P05164-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MPO	ENST00000225275.4 link	c.1365+86G>A	intron_variant	Intron 8 of 11	1	NM_000250.2	ENSP00000225275.3	P05164-1
MPO	ENST00000578493.2 link	n.698+86G>A	intron_variant	Intron 3 of 6	3
MPO	ENST00000699291.1 link	n.491-1787G>A	intron_variant	Intron 2 of 5			ENSP00000514272.1	A0A8V8TPE5

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3562

AN:

152144

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0815

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.00231

AC:

3227

AN:

1395632

Hom.:

108

AF XY:

0.00194

AC XY:

1350

AN XY:

697618

show subpopulations

African (AFR)

AF:

0.0796

AC:

2565

AN:

32206

American (AMR)

AF:

0.00465

AC:

205

AN:

44120

Ashkenazi Jewish (ASJ)

AF:

0.00136

AC:

AN:

25664

East Asian (EAS)

AF:

0.00

AC:

AN:

39360

South Asian (SAS)

AF:

0.000201

AC:

AN:

84496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52760

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

4842

European-Non Finnish (NFE)

AF:

0.0000987

AC:

104

AN:

1054158

Other (OTH)

AF:

0.00491

AC:

285

AN:

58026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

160

320

481

641

801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0235

AC:

3576

AN:

152262

Hom.:

144

Cov.:

AF XY:

0.0226

AC XY:

1684

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0816

AC:

3389

AN:

41536

American (AMR)

AF:

0.00863

AC:

132

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68014

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

165

330

494

659

824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0130

Hom.:

Bravo

AF:

0.0267

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.74

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism

(source)

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

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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