rs4251864

Positions:

• chr19-43658081-A-G

Variant summary

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

The NM_002659.4(PLAUR):​c.311-1441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,684 control chromosomes in the GnomAD database, including 2,241 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 0.15 (2241 hom., cov: 32)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.311-1441T>C		intron_variant		ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.311-1441T>C		intron_variant		1	NM_002659.4	ENSP00000339328	P1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22700 AN: 151568 Hom.: 2234 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.150 AC: 22725 AN: 151684 Hom.: 2241 Cov.: 32 AF XY: 0.151 AC XY: 11194 AN XY: 74176

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0990 Hom.: 1066

Bravo AF: 0.156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.68

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: rs4251864; hg19: chr19-44162233;