rs2239372

Variant names:

• chr19-43658802-A-G
• rs2239372
• NM_002659.4:c.311-2162T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002659.4(PLAUR):​c.311-2162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,960 control chromosomes in the GnomAD database, including 24,597 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 0.56 (24597 hom., cov: 32)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 16 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 (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.311-2162T>C		intron_variant	Intron 3 of 6	ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.311-2162T>C		intron_variant	Intron 3 of 6	1	NM_002659.4	ENSP00000339328.3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85318 AN: 151842 Hom.: 24561 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.562 AC: 85399 AN: 151960 Hom.: 24597 Cov.: 32 AF XY: 0.560 AC XY: 41573 AN XY: 74264

African (AFR) AF: 0.699 AC: 28966 AN: 41448

American (AMR) AF: 0.557 AC: 8495 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1791 AN: 3466

East Asian (EAS) AF: 0.632 AC: 3268 AN: 5170

South Asian (SAS) AF: 0.491 AC: 2363 AN: 4810

European-Finnish (FIN) AF: 0.455 AC: 4797 AN: 10550

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33903 AN: 67950

Other (OTH) AF: 0.594 AC: 1255 AN: 2112

Alfa AF: 0.528 Hom.: 39176

Bravo AF: 0.580

Asia WGS AF: 0.555 AC: 1935 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	3.2
DANN	Benign	0.52
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2239372; hg19: chr19-44162954;