NM_002659.4:c.310+1187G>A

Variant names:

• chr19-43664129-C-T
• rs2239374
• NM_002659.4:c.310+1187G>A

Variant summary

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

The NM_002659.4(PLAUR):​c.310+1187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,972 control chromosomes in the GnomAD database, including 8,027 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 0.30 (8027 hom., cov: 31)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52
• Publications: 13 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.310+1187G>A		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.310+1187G>A		intron_variant	Intron 3 of 6	1	NM_002659.4	ENSP00000339328.3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45000 AN: 151854 Hom.: 8001 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.297 AC: 45074 AN: 151972 Hom.: 8027 Cov.: 31 AF XY: 0.297 AC XY: 22052 AN XY: 74252

African (AFR) AF: 0.464 AC: 19237 AN: 41448

American (AMR) AF: 0.347 AC: 5287 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3470

East Asian (EAS) AF: 0.571 AC: 2947 AN: 5158

South Asian (SAS) AF: 0.230 AC: 1107 AN: 4804

European-Finnish (FIN) AF: 0.197 AC: 2078 AN: 10574

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13061 AN: 67948

Other (OTH) AF: 0.274 AC: 579 AN: 2112

Alfa AF: 0.229 Hom.: 8784

Bravo AF: 0.315

Asia WGS AF: 0.401 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.024
DANN	Benign	0.74
PhyloP100		-3.5
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: rs2239374; hg19: chr19-44168281;