Variant 17-58270761-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000250.2(MPO):c.2133C>T(p.Thr711Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,614,142 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 48 hom. )

Consequence

MPO
NM_000250.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.25

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:

MPO (HGNC:):

MPO links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 17-58270761-G-A is Benign according to our data. Variant chr17-58270761-G-A is described in ClinVar as [Benign]. Clinvar id is 710279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-58270761-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.25 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00292 (445/152328) while in subpopulation SAS AF= 0.0209 (101/4828). AF 95% confidence interval is 0.0176. There are 1 homozygotes in gnomad4. There are 232 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPO	NM_000250.2 linkuse as main transcript	c.2133C>T	p.Thr711Thr	synonymous_variant	12/12	ENST00000225275.4	NP_000241.1	P05164-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4 linkuse as main transcript	c.2133C>T	p.Thr711Thr	synonymous_variant	12/12	1	NM_000250.2	ENSP00000225275.3		P05164-1

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

448

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00409

AC:

1027

AN:

251260

Hom.:

AF XY:

0.00516

AC XY:

701

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0182

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00318

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00436

AC:

6372

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

3591

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0175

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00391

Gnomad4 OTH exome

AF:

0.00492

GnomAD4 genome

AF:

0.00292

AC:

445

AN:

152328

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

232

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00379

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00279

Hom.:

Bravo

AF:

0.00224

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00469

EpiControl

AF:

0.00468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.33

DANN

Benign

0.87

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

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