dbSNP rs2856857: MPO:c.155-13C>T (chr17-58280472-G-A) – 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.155-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,668 control chromosomes in the GnomAD database, including 17,658 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 0.11 ( 1280 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16378 hom. )

Consequence

MPO
NM_000250.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.284

Publications

13 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:

Genome browser will be placed here

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=-0.68).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPO	NM_000250.2 link	c.155-13C>T		intron_variant	Intron 1 of 11	ENST00000225275.4	NP_000241.1	P05164-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4 link	c.155-13C>T		intron_variant	Intron 1 of 11	1	NM_000250.2	ENSP00000225275.3		P05164-1
MPO	ENST00000580005.1 link	n.84-13C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17335

AN:

152108

Hom.:

1279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0348

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.147

GnomAD2 exomes

AF:

0.116

AC:

28913

AN:

249738

AF XY:

0.117

show subpopulations

Gnomad AFR exome

AF:

0.0336

Gnomad AMR exome

AF:

0.0891

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.143

AC:

209038

AN:

1461442

Hom.:

16378

Cov.:

AF XY:

0.140

AC XY:

101992

AN XY:

727014

show subpopulations

African (AFR)

AF:

0.0314

AC:

1050

AN:

33462

American (AMR)

AF:

0.0946

AC:

4227

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4236

AN:

26130

East Asian (EAS)

AF:

0.000302

AC:

AN:

39672

South Asian (SAS)

AF:

0.0404

AC:

3482

AN:

86230

European-Finnish (FIN)

AF:

0.154

AC:

8226

AN:

53386

Middle Eastern (MID)

AF:

0.149

AC:

860

AN:

5764

European-Non Finnish (NFE)

AF:

0.161

AC:

178615

AN:

1111722

Other (OTH)

AF:

0.138

AC:

8330

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

10533

21066

31600

42133

52666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6160

12320

18480

24640

30800

<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:

0.114

AC:

17333

AN:

152226

Hom.:

1280

Cov.:

AF XY:

0.112

AC XY:

8308

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0361

AC:

1502

AN:

41550

American (AMR)

AF:

0.130

AC:

1991

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

594

AN:

3470

East Asian (EAS)

AF:

0.000774

AC:

AN:

5166

South Asian (SAS)

AF:

0.0354

AC:

171

AN:

4826

European-Finnish (FIN)

AF:

0.151

AC:

1599

AN:

10610

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10974

AN:

67998

Other (OTH)

AF:

0.145

AC:

307

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

765

1530

2296

3061

3826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.105

Hom.:

306

Bravo

AF:

0.112

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.8

(source)

DANN

Benign

0.64

PhyloP100

-0.28

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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