rs4251883

chr19-43655667-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.473-94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,118,122 control chromosomes in the GnomAD database, including 5,386 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 (1355 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4031 hom.)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAUR	NM_002659.4	c.473-94A>G		intron_variant		ENST00000340093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAUR	ENST00000340093.8	c.473-94A>G		intron_variant		1	NM_002659.4	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16984 AN: 152174 Hom.: 1348 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0790 AC: 76328 AN: 965830 Hom.: 4031 AF XY: 0.0835 AC XY: 40415 AN XY: 484142

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.0585

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.0361

Gnomad4 NFE exome AF: 0.0637

Gnomad4 OTH exome AF: 0.0931

GnomAD4 genome AF: 0.112 AC: 17027 AN: 152292 Hom.: 1355 Cov.: 32 AF XY: 0.113 AC XY: 8409 AN XY: 74480

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0664

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0329

Gnomad4 NFE AF: 0.0644

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0951 Hom.: 219

Bravo AF: 0.116

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.3
Dann	Benign	0.48

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: rs4251883; hg19: chr19-44159819;