rs4251953

Variant names:

• chr19-43647373-C-T
• rs4251953
• ENST00000339082.7:c.755-825G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000308028 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLAUR	NM_001005376.3	c.755-825G>A		intron_variant	Intron 6 of 6		NP_001005376.1
PLAUR	XM_047438925.1	c.*321-825G>A		intron_variant	Intron 7 of 7		XP_047294881.1
PLAUR	XM_017026872.3	c.*321-825G>A		intron_variant	Intron 7 of 7		XP_016882361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000339082.7	c.755-825G>A		intron_variant	Intron 6 of 6	1		ENSP00000342049.2
ENSG00000308028	ENST00000830541.1	n.91+7356C>T		intron_variant	Intron 1 of 1
ENSG00000308028	ENST00000830542.1	n.50+7291C>T		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.0411 AC: 1706 AN: 41536

American (AMR) AF: 0.0515 AC: 787 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0280 AC: 135 AN: 4822

European-Finnish (FIN) AF: 0.0713 AC: 756 AN: 10608

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.0520 AC: 3536 AN: 68018

Other (OTH) AF: 0.0634 AC: 134 AN: 2114

Alfa AF: 0.0531 Hom.: 116

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
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4251953; hg19: chr19-44151525;