rs2286960

Positions:

• chr19-43667873-C-T

Variant summary

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

The NM_002659.4(PLAUR):​c.56-182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,429,350 control chromosomes in the GnomAD database, including 39,596 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 0.23 (4134 hom., cov: 31)
  • Exomes 𝑓: 0.23 (35462 hom.)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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 (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.56-182G>A		intron_variant		ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.56-182G>A		intron_variant		1	NM_002659.4	ENSP00000339328	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34670 AN: 151902 Hom.: 4135 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0823

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.231 AC: 295444 AN: 1277330 Hom.: 35462 Cov.: 31 AF XY: 0.231 AC XY: 142873 AN XY: 618104

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.0892

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.228 AC: 34680 AN: 152020 Hom.: 4134 Cov.: 31 AF XY: 0.223 AC XY: 16562 AN XY: 74312

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.0821

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.248

Alfa AF: 0.229 Hom.: 5835

Bravo AF: 0.232

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.78

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: rs2286960; hg19: chr19-44172025; COSMIC: COSV55389636; COSMIC: COSV55389636;