NM_000250.2:c.155-13C>T

Variant names:

• chr17-58280472-G-A
• rs2856857
• NM_000250.2:c.155-13C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 13 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPO	NM_000250.2	MANE Select	c.155-13C>T		intron	N/A	NP_000241.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPO	ENST00000225275.4	TSL:1 MANE Select	c.155-13C>T		intron	N/A	ENSP00000225275.3
	MPO	ENST00000580005.1	TSL:3	n.84-13C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17335 AN: 152108 Hom.: 1279 Cov.: 32

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

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.: 33 AF XY: 0.140 AC XY: 101992 AN XY: 727014

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: 12 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

GnomAD4 genome AF: 0.114 AC: 17333 AN: 152226 Hom.: 1280 Cov.: 32 AF XY: 0.112 AC XY: 8308 AN XY: 74414

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: 4 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: 47 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10974 AN: 67998

Other (OTH) AF: 0.145 AC: 307 AN: 2116

Alfa AF: 0.105 Hom.: 306

Bravo AF: 0.112

Asia WGS AF: 0.0220 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.8
DANN	Benign	0.64
PhyloP100		-0.28
PromoterAI		0.014	Neutral
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: rs2856857; hg19: chr17-56357833;