chr17-58270761-G-A

Variant names:

• chr17-58270761-G-A
• rs61747608
• NM_000250.2:c.2133C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.25
• Publications: 3 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 -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 VariationId is 710279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 48 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000250.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPO	NM_000250.2	MANE Select	c.2133C>T	p.Thr711Thr	synonymous	Exon 12 of 12	NP_000241.1	P05164-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPO	ENST00000225275.4	TSL:1 MANE Select	c.2133C>T	p.Thr711Thr	synonymous	Exon 12 of 12	ENSP00000225275.3	P05164-1
	MPO	ENST00000577220.1	TSL:3	c.228C>T	p.Thr76Thr	synonymous	Exon 3 of 3	ENSP00000464668.1	J3QSF7
	MPO	ENST00000578493.2	TSL:3	n.1466C>T		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.00294 AC: 448 AN: 152210 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.00409 AC: 1027 AN: 251260 AF XY: 0.00516

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 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

African (AFR) AF: 0.000627 AC: 21 AN: 33478

American (AMR) AF: 0.00159 AC: 71 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 50 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0175 AC: 1510 AN: 86258

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53420

Middle Eastern (MID) AF: 0.0104 AC: 60 AN: 5762

European-Non Finnish (NFE) AF: 0.00391 AC: 4348 AN: 1111946

Other (OTH) AF: 0.00492 AC: 297 AN: 60394

GnomAD4 genome AF: 0.00292 AC: 445 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.00311 AC XY: 232 AN XY: 74484

African (AFR) AF: 0.000890 AC: 37 AN: 41584

American (AMR) AF: 0.00163 AC: 25 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0209 AC: 101 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00379 AC: 258 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.33
DANN	Benign	0.87
PhyloP100		-3.2
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs61747608; hg19: chr17-56348122;