17-58275456-C-T

Position:

• chr17-58275456-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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=-0.83).
• 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/exons	MANE	UniProt
MPO	NM_000250.2	c.1365+86G>A		intron_variant		ENST00000225275.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPO	ENST00000225275.4	c.1365+86G>A		intron_variant		1	NM_000250.2	P1
MPO	ENST00000699291.1	c.491-1787G>A		intron_variant, NMD_transcript_variant
MPO	ENST00000578493.2	n.698+86G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3562 AN: 152144 Hom.: 143 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0796

Gnomad4 AMR exome AF: 0.00465

Gnomad4 ASJ exome AF: 0.00136

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000987

Gnomad4 OTH exome AF: 0.00491

GnomAD4 genome AF: 0.0235 AC: 3576 AN: 152262 Hom.: 144 Cov.: 32 AF XY: 0.0226 AC XY: 1684 AN XY: 74458

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.00863

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0105 Hom.: 10

Bravo AF: 0.0267

Asia WGS AF: 0.00577 AC: 20 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
DANN	Benign	0.74

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: rs8067377; hg19: chr17-56352817;