Variant 17-58270869-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000250.2(MPO):c.2031-6A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,612,414 control chromosomes in the GnomAD database, including 19,702 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1685 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18017 hom. )

Consequence

MPO
NM_000250.2 splice_region, intron

Scores

Splicing: ADA: 0.00003099

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 17-58270869-T-G is Benign according to our data. Variant chr17-58270869-T-G is described in ClinVar as [Benign]. Clinvar id is 403102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-58270869-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPO	NM_000250.2 link	c.2031-6A>C		splice_region_variant, intron_variant		ENST00000225275.4	NP_000241.1	P05164-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4 link	c.2031-6A>C		splice_region_variant, intron_variant		1	NM_000250.2	ENSP00000225275.3		P05164-1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22744

AN:

151950

Hom.:

1681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.0952

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.146

AC:

36548

AN:

251030

Hom.:

2762

AF XY:

0.149

AC XY:

20208

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0871

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.165

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.156

AC:

227356

AN:

1460346

Hom.:

18017

Cov.:

AF XY:

0.157

AC XY:

113728

AN XY:

726494

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.0940

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.0835

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

AF:

0.150

AC:

22752

AN:

152068

Hom.:

1685

Cov.:

AF XY:

0.149

AC XY:

11098

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.0954

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.154

Hom.:

3019

Bravo

AF:

0.146

Asia WGS

AF:

0.122

AC:

423

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

MPO-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.022

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.030

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over