rs11649901

Positions:

• chr17-58274455-A-G
• chr17-58274455-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000250.2(MPO):​c.1366-786T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,524 control chromosomes in the GnomAD database, including 12,390 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 0.39 (12390 hom., cov: 29)
• Consequence: MPO NM_000250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPO	NM_000250.2	c.1366-786T>C		intron_variant		ENST00000225275.4	NP_000241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4	c.1366-786T>C		intron_variant		1	NM_000250.2	ENSP00000225275	P1
MPO	ENST00000699291.1	c.491-786T>C		intron_variant, NMD_transcript_variant				ENSP00000514272
MPO	ENST00000578493.2	n.699-786T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58526 AN: 151410 Hom.: 12371 Cov.: 29

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.387 AC: 58582 AN: 151524 Hom.: 12390 Cov.: 29 AF XY: 0.381 AC XY: 28204 AN XY: 74032

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.402

Alfa AF: 0.368 Hom.: 4034

Bravo AF: 0.398

Asia WGS AF: 0.183 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs11649901; hg19: chr17-56351816;