19-43668036-T-C

Variant names:

• chr19-43668036-T-C
• rs344783
• NM_002659.4:c.56-345A>G

Variant summary

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

The NM_002659.4(PLAUR):​c.56-345A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,077,484 control chromosomes in the GnomAD database, including 152,892 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 0.54 (22501 hom., cov: 29)
  • Exomes 𝑓: 0.53 (130391 hom.)
• Consequence: PLAUR NM_002659.4 intron
• Scores: Splicing: ADA: 0.0001889
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.56-345A>G		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.56-345A>G		intron_variant	Intron 1 of 6	1	NM_002659.4	ENSP00000339328.3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82391 AN: 151496 Hom.: 22468 Cov.: 29

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.529 AC: 489822 AN: 925870 Hom.: 130391 Cov.: 35 AF XY: 0.528 AC XY: 229462 AN XY: 434694

African (AFR) AF: 0.578 AC: 10950 AN: 18934

American (AMR) AF: 0.529 AC: 2860 AN: 5408

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 3493 AN: 7632

East Asian (EAS) AF: 0.436 AC: 3430 AN: 7872

South Asian (SAS) AF: 0.474 AC: 14761 AN: 31142

European-Finnish (FIN) AF: 0.531 AC: 2317 AN: 4360

Middle Eastern (MID) AF: 0.508 AC: 1715 AN: 3378

European-Non Finnish (NFE) AF: 0.532 AC: 433385 AN: 814666

Other (OTH) AF: 0.521 AC: 16911 AN: 32478

GnomAD4 genome AF: 0.544 AC: 82489 AN: 151614 Hom.: 22501 Cov.: 29 AF XY: 0.543 AC XY: 40206 AN XY: 74048

African (AFR) AF: 0.573 AC: 23679 AN: 41294

American (AMR) AF: 0.543 AC: 8261 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2362 AN: 5120

South Asian (SAS) AF: 0.481 AC: 2308 AN: 4796

European-Finnish (FIN) AF: 0.558 AC: 5880 AN: 10530

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.541 AC: 36742 AN: 67870

Other (OTH) AF: 0.538 AC: 1135 AN: 2110

Alfa AF: 0.536 Hom.: 91638

Bravo AF: 0.543

Asia WGS AF: 0.477 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.39
PhyloP100		-0.54
PromoterAI		0.058	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.0020
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: rs344783; hg19: chr19-44172188; COSMIC: COSV55390828; COSMIC: COSV55390828;