19-43648948-A-G

Variant names:

• chr19-43648948-A-G
• rs4760
• NM_002659.4:c.950T>C

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 66 publications found

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]

ENSG00000308028 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	NM_002659.4	MANE Select	c.950T>C	p.Leu317Pro	missense	Exon 7 of 7	NP_002650.1
	PLAUR	NM_001005377.3		c.815T>C	p.Leu272Pro	missense	Exon 6 of 6	NP_001005377.1
	PLAUR	NM_001301037.2		c.803T>C	p.Leu268Pro	missense	Exon 6 of 6	NP_001287966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	ENST00000340093.8	TSL:1 MANE Select	c.950T>C	p.Leu317Pro	missense	Exon 7 of 7	ENSP00000339328.3
	PLAUR	ENST00000221264.8	TSL:1	c.815T>C	p.Leu272Pro	missense	Exon 6 of 6	ENSP00000221264.3
	PLAUR	ENST00000601723.5	TSL:1	c.803T>C	p.Leu268Pro	missense	Exon 6 of 6	ENSP00000471881.1

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

GnomAD2 exomes AF: 0.121 AC: 30428 AN: 251374 AF XY: 0.126

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 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

African (AFR) AF: 0.0203 AC: 680 AN: 33480

American (AMR) AF: 0.0816 AC: 3651 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 1957 AN: 26126

East Asian (EAS) AF: 0.000982 AC: 39 AN: 39700

South Asian (SAS) AF: 0.138 AC: 11925 AN: 86248

European-Finnish (FIN) AF: 0.171 AC: 9129 AN: 53418

Middle Eastern (MID) AF: 0.0778 AC: 448 AN: 5758

European-Non Finnish (NFE) AF: 0.157 AC: 175014 AN: 1111756

Other (OTH) AF: 0.119 AC: 7213 AN: 60390

GnomAD4 genome AF: 0.108 AC: 16406 AN: 152214 Hom.: 1206 Cov.: 31 AF XY: 0.108 AC XY: 8006 AN XY: 74412

African (AFR) AF: 0.0250 AC: 1040 AN: 41554

American (AMR) AF: 0.0940 AC: 1438 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5174

South Asian (SAS) AF: 0.133 AC: 640 AN: 4812

European-Finnish (FIN) AF: 0.177 AC: 1881 AN: 10606

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10736 AN: 67990

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.131 Hom.: 4541

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 v4.9

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
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.043
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.54
MPC		0.74
ClinPred		0.023	T
GERP RS		2.9
Varity_R		0.45
gMVP		0.90
Mutation Taster		=88/12	polymorphism (auto)

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: rs4760; hg19: chr19-44153100; COSMIC: COSV107281313; COSMIC: COSV107281313;