rs2071409

Variant names:

• chr17-58270869-T-G
• rs2071409
• NM_000250.2:c.2031-6A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-58270869-T-G
• chr17-58270869-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Publications: 34 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 -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 VariationId is 403102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

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.2031-6A>C		splice_region intron	N/A	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.2031-6A>C		splice_region intron	N/A	ENSP00000225275.3	P05164-1
	MPO	ENST00000577220.1	TSL:3	c.184-64A>C		intron	N/A	ENSP00000464668.1	J3QSF7
	MPO	ENST00000578493.2	TSL:3	n.1364-6A>C		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22744 AN: 151950 Hom.: 1681 Cov.: 32

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

GnomAD2 exomes AF: 0.146 AC: 36548 AN: 251030 AF XY: 0.149

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 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.: 32 AF XY: 0.157 AC XY: 113728 AN XY: 726494

African (AFR) AF: 0.140 AC: 4664 AN: 33430

American (AMR) AF: 0.0940 AC: 4206 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4864 AN: 26132

East Asian (EAS) AF: 0.0835 AC: 3316 AN: 39698

South Asian (SAS) AF: 0.166 AC: 14311 AN: 86198

European-Finnish (FIN) AF: 0.160 AC: 8556 AN: 53412

Middle Eastern (MID) AF: 0.163 AC: 768 AN: 4712

European-Non Finnish (NFE) AF: 0.159 AC: 177099 AN: 1111780

Other (OTH) AF: 0.159 AC: 9572 AN: 60262

GnomAD4 genome AF: 0.150 AC: 22752 AN: 152068 Hom.: 1685 Cov.: 32 AF XY: 0.149 AC XY: 11098 AN XY: 74344

African (AFR) AF: 0.144 AC: 5974 AN: 41482

American (AMR) AF: 0.122 AC: 1868 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3466

East Asian (EAS) AF: 0.0954 AC: 493 AN: 5168

South Asian (SAS) AF: 0.166 AC: 797 AN: 4810

European-Finnish (FIN) AF: 0.159 AC: 1685 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10813 AN: 67970

Other (OTH) AF: 0.157 AC: 331 AN: 2110

Alfa AF: 0.153 Hom.: 3629

Bravo AF: 0.146

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	MPO-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.022
DANN	Benign	0.74
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071409; hg19: chr17-56348230; COSMIC: COSV51857523; COSMIC: COSV51857523;