Genetic Variant NM_000250.2:c.-310G>A (chr17-58281068-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.667

Variant links:

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]

MPO links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.-310G>A		upstream_gene_variant		ENST00000225275.4	NP_000241.1	P05164-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4 link	c.-310G>A		upstream_gene_variant		1	NM_000250.2	ENSP00000225275.3		P05164-1

Frequencies

GnomAD3 genomes

AF:

0.0425

AC:

6422

AN:

151144

Hom.:

190

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.00554

Gnomad4 AMR exome

AF:

0.0234

Gnomad4 ASJ exome

AF:

0.0359

Gnomad4 EAS exome

AF:

0.000159

Gnomad4 SAS exome

AF:

0.00428

Gnomad4 FIN exome

AF:

0.0610

Gnomad4 NFE exome

AF:

0.0429

Gnomad4 OTH exome

AF:

0.0337

GnomAD4 genome

AF:

0.0425

AC:

6423

AN:

151202

Hom.:

190

Cov.:

AF XY:

0.0438

AC XY:

3228

AN XY:

73746

show subpopulations

Gnomad4 AFR

AF:

0.00949

Gnomad4 AMR

AF:

0.0380

Gnomad4 ASJ

AF:

0.0531

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00669

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.0587

Gnomad4 OTH

AF:

0.0361

Alfa

AF:

0.0485

Hom.:

Bravo

AF:

0.0372

Asia WGS

AF:

0.00433

AC:

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over