rs4251953

Positions:

• chr19-43647373-C-T

Variant summary

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

The ENST00000339082.7(PLAUR):​c.755-825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 152,226 control chromosomes in the GnomAD database, including 198 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 0.048 (198 hom., cov: 31)
• Consequence: PLAUR ENST00000339082.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAUR	NM_001005376.3	c.755-825G>A		intron_variant			NP_001005376.1
PLAUR	XM_017026872.3	c.*321-825G>A		intron_variant			XP_016882361.1
PLAUR	XM_047438925.1	c.*321-825G>A		intron_variant			XP_047294881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000339082.7	c.755-825G>A		intron_variant		1		ENSP00000342049

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7330 AN: 152108 Hom.: 198 Cov.: 31

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0482 AC: 7331 AN: 152226 Hom.: 198 Cov.: 31 AF XY: 0.0493 AC XY: 3672 AN XY: 74422

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0280

Gnomad4 FIN AF: 0.0713

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0549 Hom.: 81

Bravo AF: 0.0479

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4251953; hg19: chr19-44151525;