rs4760

chr19-43648948-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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]

ACMG classification

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	UniProt
PLAUR	NM_002659.4	c.950T>C	p.Leu317Pro	missense_variant	7/7	ENST00000340093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAUR	ENST00000340093.8	c.950T>C	p.Leu317Pro	missense_variant	7/7	1	NM_002659.4	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16400 AN: 152096 Hom.: 1204 Cov.: 31

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

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.: 33 AF XY: 0.145 AC XY: 105214 AN XY: 727082

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.: 31 AF XY: 0.108 AC XY: 8006 AN XY: 74412

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	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;.
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.73	T;T;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.92	P;P;P
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.99, 0.99	.;D;D
Vest4		0.54
MPC		0.74
ClinPred		0.023	T
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

Other links and lift over

dbSNP: rs4760; hg19: chr19-44153100;