17-58280457-C-A

Variant names:

• chr17-58280457-C-A
• rs7208693
• NM_000250.2:c.157G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000250.2(MPO):​c.157G>T​(p.Val53Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 1,613,748 control chromosomes in the GnomAD database, including 6,252 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1082 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5170 hom.)
• Consequence: MPO NM_000250.2 missense, splice_region
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0440
• Publications: 45 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012850165).
• BP6: Variant 17-58280457-C-A is Benign according to our data. Variant chr17-58280457-C-A is described in ClinVar as Benign. ClinVar VariationId is 3055447.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 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.157G>T	p.Val53Phe	missense splice_region	Exon 2 of 12	NP_000241.1	P05164-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPO	ENST00000225275.4	TSL:1 MANE Select	c.157G>T	p.Val53Phe	missense splice_region	Exon 2 of 12	ENSP00000225275.3	P05164-1
	MPO	ENST00000580005.1	TSL:3	n.86G>T		splice_region non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16466 AN: 152042 Hom.: 1078 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.0860

GnomAD2 exomes AF: 0.0895 AC: 22421 AN: 250438 AF XY: 0.0851

Gnomad AFR exome AF: 0.184

Gnomad AMR exome AF: 0.0855

Gnomad ASJ exome AF: 0.0331

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.0732

Gnomad OTH exome AF: 0.0720

GnomAD4 exome AF: 0.0786 AC: 114847 AN: 1461586 Hom.: 5170 Cov.: 32 AF XY: 0.0775 AC XY: 56331 AN XY: 727084

African (AFR) AF: 0.190 AC: 6347 AN: 33470

American (AMR) AF: 0.0838 AC: 3746 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 871 AN: 26136

East Asian (EAS) AF: 0.126 AC: 5018 AN: 39690

South Asian (SAS) AF: 0.0789 AC: 6801 AN: 86236

European-Finnish (FIN) AF: 0.119 AC: 6334 AN: 53406

Middle Eastern (MID) AF: 0.0300 AC: 173 AN: 5768

European-Non Finnish (NFE) AF: 0.0728 AC: 80936 AN: 1111802

Other (OTH) AF: 0.0765 AC: 4621 AN: 60378

GnomAD4 genome AF: 0.108 AC: 16491 AN: 152162 Hom.: 1082 Cov.: 32 AF XY: 0.109 AC XY: 8136 AN XY: 74376

African (AFR) AF: 0.183 AC: 7574 AN: 41492

American (AMR) AF: 0.0686 AC: 1049 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3472

East Asian (EAS) AF: 0.118 AC: 606 AN: 5154

South Asian (SAS) AF: 0.0859 AC: 415 AN: 4832

European-Finnish (FIN) AF: 0.124 AC: 1319 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5156 AN: 67986

Other (OTH) AF: 0.0865 AC: 183 AN: 2116

Alfa AF: 0.0801 Hom.: 2422

Bravo AF: 0.108

TwinsUK AF: 0.0750 AC: 278

ALSPAC AF: 0.0714 AC: 275

ESP6500AA AF: 0.184 AC: 812

ESP6500EA AF: 0.0726 AC: 624

ExAC AF: 0.0913 AC: 11080

Asia WGS AF: 0.114 AC: 395 AN: 3478

EpiCase AF: 0.0604

EpiControl AF: 0.0639

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MPO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.8
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.044
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.072
Sift	Benign	0.25	T
Sift4G	Benign	0.45	T
Polyphen		0.086	B
Vest4		0.12
MPC		0.46
ClinPred		0.0018	T
GERP RS		-1.8
PromoterAI		-0.00060	Neutral
Varity_R		0.077
gMVP		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7208693; hg19: chr17-56357818; COSMIC: COSV56563158; COSMIC: COSV56563158;