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GeneBe

17-58270761-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000250.2(MPO):c.2133C>T(p.Thr711=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars. Variant chr17-58270761-G-A is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.25 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MPONM_000250.2 linkuse as main transcriptc.2133C>T p.Thr711= synonymous_variant 12/12 ENST00000225275.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MPOENST00000225275.4 linkuse as main transcriptc.2133C>T p.Thr711= synonymous_variant 12/121 NM_000250.2 P1P05164-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00294
AC:
448
AN:
152210
Hom.:
1
Cov.:
32
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.:
10
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.:
48
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00292
AC:
445
AN:
152328
Hom.:
1
Cov.:
32
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.:
0
Bravo
AF:
0.00224
Asia WGS
AF:
0.00433
AC:
15
AN:
3478
EpiCase
AF:
0.00469
EpiControl
AF:
0.00468

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 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.

Other links and lift over

dbSNP: rs61747608; hg19: chr17-56348122; API