rs2286960

Variant names:

• chr19-43667873-C-T
• rs2286960
• NM_002659.4:c.56-182G>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.56-182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,429,350 control chromosomes in the GnomAD database, including 39,596 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 0.23 (4134 hom., cov: 31)
  • Exomes 𝑓: 0.23 (35462 hom.)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 14 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.56-182G>A		intron_variant	Intron 1 of 6	ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.56-182G>A		intron_variant	Intron 1 of 6	1	NM_002659.4	ENSP00000339328.3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34670 AN: 151902 Hom.: 4135 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0823

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.231 AC: 295444 AN: 1277330 Hom.: 35462 Cov.: 31 AF XY: 0.231 AC XY: 142873 AN XY: 618104

African (AFR) AF: 0.269 AC: 7709 AN: 28618

American (AMR) AF: 0.161 AC: 3607 AN: 22466

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 6122 AN: 18856

East Asian (EAS) AF: 0.0892 AC: 3031 AN: 33964

South Asian (SAS) AF: 0.190 AC: 12065 AN: 63390

European-Finnish (FIN) AF: 0.176 AC: 5226 AN: 29628

Middle Eastern (MID) AF: 0.283 AC: 1468 AN: 5182

European-Non Finnish (NFE) AF: 0.238 AC: 243709 AN: 1022264

Other (OTH) AF: 0.236 AC: 12507 AN: 52962

GnomAD4 genome AF: 0.228 AC: 34680 AN: 152020 Hom.: 4134 Cov.: 31 AF XY: 0.223 AC XY: 16562 AN XY: 74312

African (AFR) AF: 0.265 AC: 11004 AN: 41460

American (AMR) AF: 0.201 AC: 3057 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3470

East Asian (EAS) AF: 0.0821 AC: 425 AN: 5178

South Asian (SAS) AF: 0.182 AC: 878 AN: 4828

European-Finnish (FIN) AF: 0.163 AC: 1728 AN: 10580

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15518 AN: 67952

Other (OTH) AF: 0.248 AC: 523 AN: 2108

Alfa AF: 0.232 Hom.: 9022

Bravo AF: 0.232

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.78
PhyloP100		0.19
PromoterAI		0.0090	Neutral
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: rs2286960; hg19: chr19-44172025; COSMIC: COSV55389636; COSMIC: COSV55389636;