17-58281068-C-T

Variant names:

• chr17-58281068-C-T
• rs34097845
• NM_000250.2:c.-310G>A

Variant summary

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

The NM_000250.2(MPO):​c.-310G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 354,834 control chromosomes in the GnomAD database, including 425 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 0.042 (190 hom., cov: 32)
  • Exomes 𝑓: 0.034 (235 hom.)
• Consequence: MPO NM_000250.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPO	NM_000250.2	c.-310G>A		upstream_gene_variant		ENST00000225275.4	NP_000241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4	c.-310G>A		upstream_gene_variant		1	NM_000250.2	ENSP00000225275.3

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6422 AN: 151144 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.00951

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00627

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0131

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0340 AC: 6918 AN: 203632 Hom.: 235 AF XY: 0.0312 AC XY: 3310 AN XY: 106128

African (AFR) AF: 0.00554 AC: 37 AN: 6680

American (AMR) AF: 0.0234 AC: 178 AN: 7612

Ashkenazi Jewish (ASJ) AF: 0.0359 AC: 231 AN: 6442

East Asian (EAS) AF: 0.000159 AC: 2 AN: 12550

South Asian (SAS) AF: 0.00428 AC: 99 AN: 23150

European-Finnish (FIN) AF: 0.0610 AC: 659 AN: 10800

Middle Eastern (MID) AF: 0.00962 AC: 9 AN: 936

European-Non Finnish (NFE) AF: 0.0429 AC: 5295 AN: 123370

Other (OTH) AF: 0.0337 AC: 408 AN: 12092

GnomAD4 genome AF: 0.0425 AC: 6423 AN: 151202 Hom.: 190 Cov.: 32 AF XY: 0.0438 AC XY: 3228 AN XY: 73746

African (AFR) AF: 0.00949 AC: 391 AN: 41184

American (AMR) AF: 0.0380 AC: 578 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00669 AC: 32 AN: 4780

European-Finnish (FIN) AF: 0.104 AC: 1058 AN: 10220

Middle Eastern (MID) AF: 0.0141 AC: 4 AN: 284

European-Non Finnish (NFE) AF: 0.0587 AC: 3988 AN: 67908

Other (OTH) AF: 0.0361 AC: 75 AN: 2080

Alfa AF: 0.0485 Hom.: 18

Bravo AF: 0.0372

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.53
PhyloP100		-0.67
PromoterAI		-0.053	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34097845; hg19: chr17-56358429;