chr17-58275456-C-A

Variant names:

• chr17-58275456-C-A
• rs8067377
• NM_000250.2:c.1365+86G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000250.2(MPO):​c.1365+86G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000086 in 1,395,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: MPO NM_000250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPO	NM_000250.2	c.1365+86G>T		intron_variant	Intron 8 of 11	ENST00000225275.4	NP_000241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4	c.1365+86G>T		intron_variant	Intron 8 of 11	1	NM_000250.2	ENSP00000225275.3
MPO	ENST00000578493.2	n.698+86G>T		intron_variant	Intron 3 of 6	3
MPO	ENST00000699291.1	n.491-1787G>T		intron_variant	Intron 2 of 5			ENSP00000514272.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000860 AC: 12 AN: 1395662 Hom.: 0 AF XY: 0.00000430 AC XY: 3 AN XY: 697632

African (AFR) AF: 0.00 AC: 0 AN: 32232

American (AMR) AF: 0.00 AC: 0 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 39360

South Asian (SAS) AF: 0.00 AC: 0 AN: 84496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4842

European-Non Finnish (NFE) AF: 0.0000104 AC: 11 AN: 1054160

Other (OTH) AF: 0.0000172 AC: 1 AN: 58026

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		0.15

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: rs8067377; hg19: chr17-56352817;