rs2283628

Positions:

• chr19-43658909-T-C

Variant summary

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

The NM_002659.4(PLAUR):​c.311-2269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,088 control chromosomes in the GnomAD database, including 5,248 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 0.25 (5248 hom., cov: 31)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAUR	NM_002659.4	c.311-2269A>G		intron_variant		ENST00000340093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAUR	ENST00000340093.8	c.311-2269A>G		intron_variant		1	NM_002659.4	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37323 AN: 151970 Hom.: 5232 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.246 AC: 37385 AN: 152088 Hom.: 5248 Cov.: 31 AF XY: 0.246 AC XY: 18300 AN XY: 74360

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.263

Alfa AF: 0.223 Hom.: 1409

Bravo AF: 0.265

Asia WGS AF: 0.405 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2283628; hg19: chr19-44163061;