rs2239374

chr19-43664129-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.310+1187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,972 control chromosomes in the GnomAD database, including 8,027 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 0.30 (8027 hom., cov: 31)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAUR	NM_002659.4	c.310+1187G>A		intron_variant		ENST00000340093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAUR	ENST00000340093.8	c.310+1187G>A		intron_variant		1	NM_002659.4	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45000 AN: 151854 Hom.: 8001 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45074 AN: 151972 Hom.: 8027 Cov.: 31 AF XY: 0.297 AC XY: 22052 AN XY: 74252

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.274

Alfa AF: 0.216 Hom.: 5507

Bravo AF: 0.315

Asia WGS AF: 0.401 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.024
Dann	Benign	0.74

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: rs2239374; hg19: chr19-44168281;