chr19-43665586-G-A

Variant names:

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_002659.4(PLAUR):c.167-127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00000614 (AC=5) in the gnomAD database across 813,734 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.000015. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

PLAUR
NM_002659.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.917

Publications

9 publications found

Variant links:

Genes affected

PLAUR (HGNC:9053): (plasminogen activator, urokinase receptor) This gene encodes the receptor for urokinase plasminogen activator and, given its role in localizing and promoting plasmin formation, likely influences many normal and pathological processes related to cell-surface plasminogen activation and localized degradation of the extracellular matrix. It binds both the proprotein and mature forms of urokinase plasminogen activator and permits the activation of the receptor-bound pro-enzyme by plasmin. The protein lacks transmembrane or cytoplasmic domains and may be anchored to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) moiety following cleavage of the nascent polypeptide near its carboxy-terminus. However, a soluble protein is also produced in some cell types. Alternative splicing results in multiple transcript variants encoding different isoforms. The proprotein experiences several post-translational cleavage reactions that have not yet been fully defined. [provided by RefSeq, Jul 2008]

PLAUR links:

ENSG00000308028 (HGNC:):

ENSG00000308028 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002659.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 points.

PM2

Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.000015 — very rare for unknown gene (threshold 0.001) — PM2 moderate.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002659.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLAUR	NM_002659.4	MANE Select	c.167-127C>T	intron	N/A	NP_002650.1	Q03405-1
PLAUR	NM_001005377.3		c.167-127C>T	intron	N/A	NP_001005377.1	Q03405-3
PLAUR	NM_001301037.2		c.167-127C>T	intron	N/A	NP_001287966.1	M0R1I2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLAUR	ENST00000340093.8	TSL:1 MANE Select	c.167-127C>T	intron	N/A	ENSP00000339328.3	Q03405-1
PLAUR	ENST00000221264.8	TSL:1	c.167-127C>T	intron	N/A	ENSP00000221264.3	Q03405-3
PLAUR	ENST00000601723.5	TSL:1	c.167-127C>T	intron	N/A	ENSP00000471881.1	M0R1I2

Frequencies

GnomAD3 genomes

AF:

0.00000687

AC:

AN:

145582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000599

AC:

AN:

668152

Hom.:

AF XY:

0.00

AC XY:

AN XY:

340996

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17310

American (AMR)

AF:

0.00

AC:

AN:

23484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14932

East Asian (EAS)

AF:

0.00

AC:

AN:

32484

South Asian (SAS)

AF:

0.00

AC:

AN:

46234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2328

European-Non Finnish (NFE)

AF:

0.00000860

AC:

AN:

465086

Other (OTH)

AF:

0.00

AC:

AN:

32362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000687

AC:

AN:

145582

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38950

American (AMR)

AF:

0.00

AC:

AN:

14150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

4856

South Asian (SAS)

AF:

0.00

AC:

AN:

4398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9818

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66828

Other (OTH)

AF:

0.00

AC:

AN:

1958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000106

Hom.:

5101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

(source)

DANN

Benign

0.91

PhyloP100

-0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over