19-43665586-G-C

Variant names:

• chr19-43665586-G-C
• rs4251831
• NM_002659.4:c.167-127C>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.167-127C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 812,094 control chromosomes in the GnomAD database, including 217,053 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 0.77 (44056 hom., cov: 19)
  • Exomes 𝑓: 0.72 (172997 hom.)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.167-127C>G		intron_variant	Intron 2 of 6	ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.167-127C>G		intron_variant	Intron 2 of 6	1	NM_002659.4	ENSP00000339328.3

Frequencies

GnomAD3 genomes AF: 0.771 AC: 111999 AN: 145358 Hom.: 44001 Cov.: 19

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.716 AC: 477041 AN: 666616 Hom.: 172997 AF XY: 0.717 AC XY: 243944 AN XY: 340218

African (AFR) AF: 0.924 AC: 15988 AN: 17300

American (AMR) AF: 0.836 AC: 19616 AN: 23462

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 11499 AN: 14908

East Asian (EAS) AF: 0.846 AC: 27480 AN: 32466

South Asian (SAS) AF: 0.760 AC: 35070 AN: 46144

European-Finnish (FIN) AF: 0.624 AC: 21132 AN: 33882

Middle Eastern (MID) AF: 0.730 AC: 1699 AN: 2328

European-Non Finnish (NFE) AF: 0.692 AC: 320818 AN: 463822

Other (OTH) AF: 0.735 AC: 23739 AN: 32304

GnomAD4 genome AF: 0.771 AC: 112114 AN: 145478 Hom.: 44056 Cov.: 19 AF XY: 0.769 AC XY: 54200 AN XY: 70440

African (AFR) AF: 0.923 AC: 36015 AN: 39038

American (AMR) AF: 0.824 AC: 11642 AN: 14124

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2645 AN: 3422

East Asian (EAS) AF: 0.845 AC: 4091 AN: 4840

South Asian (SAS) AF: 0.763 AC: 3345 AN: 4386

European-Finnish (FIN) AF: 0.611 AC: 5980 AN: 9792

Middle Eastern (MID) AF: 0.762 AC: 218 AN: 286

European-Non Finnish (NFE) AF: 0.690 AC: 46016 AN: 66720

Other (OTH) AF: 0.782 AC: 1548 AN: 1980

Alfa AF: 0.726 Hom.: 5101

Bravo AF: 0.795

Asia WGS AF: 0.834 AC: 2901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.68
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

Publications

LitVar

Other links and lift over

dbSNP: rs4251831; hg19: chr19-44169738; COSMIC: COSV55390467; COSMIC: COSV55390467;