Variant chr19-43648948-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002659.4(PLAUR):c.950T>C(p.Leu317Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,812 control chromosomes in the GnomAD database, including 17,606 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1206 hom., cov: 31)

Exomes 𝑓: 0.14 ( 16400 hom. )

Consequence

PLAUR
NM_002659.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017075837).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAUR	NM_002659.4 linkuse as main transcript	c.950T>C	p.Leu317Pro	missense_variant	7/7	ENST00000340093.8	NP_002650.1	Q03405-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8 linkuse as main transcript	c.950T>C	p.Leu317Pro	missense_variant	7/7	1	NM_002659.4	ENSP00000339328.3		Q03405-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16400

AN:

152096

Hom.:

1204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.0937

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.0952

GnomAD3 exomes

AF:

0.121

AC:

30428

AN:

251374

Hom.:

2226

AF XY:

0.126

AC XY:

17164

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0259

Gnomad AMR exome

AF:

0.0780

Gnomad ASJ exome

AF:

0.0748

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.144

AC:

210056

AN:

1461598

Hom.:

16400

Cov.:

AF XY:

0.145

AC XY:

105214

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.0816

Gnomad4 ASJ exome

AF:

0.0749

Gnomad4 EAS exome

AF:

0.000982

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.108

AC:

16406

AN:

152214

Hom.:

1206

Cov.:

AF XY:

0.108

AC XY:

8006

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0250

Gnomad4 AMR

AF:

0.0940

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.0938

Alfa

AF:

0.136

Hom.:

3355

Bravo

AF:

0.0950

TwinsUK

AF:

0.149

AC:

554

ALSPAC

AF:

0.152

AC:

585

ESP6500AA

AF:

0.0300

AC:

132

ESP6500EA

AF:

0.154

AC:

1327

ExAC

AF:

0.122

AC:

14866

Asia WGS

AF:

0.0580

AC:

204

AN:

3478

EpiCase

AF:

0.145

EpiControl

AF:

0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;.

Eigen

Benign

-0.039

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

.;N;D

REVEL

Benign

0.043

Sift

Uncertain

0.0010

.;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.99, 0.99

.;D;D

Vest4

0.54

MPC

0.74

ClinPred

0.023

GERP RS

2.9

Varity_R

0.45

gMVP

0.90

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over