rs4251805

Positions:

• chr19-43670289-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000221264.8(PLAUR):​c.-169G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 628,454 control chromosomes in the GnomAD database, including 549 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 0.043 (186 hom., cov: 32)
  • Exomes 𝑓: 0.034 (363 hom.)
• Consequence: PLAUR ENST00000221264.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847

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]

LOC124904724 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904724	XR_007067264.1	n.684C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000221264.8	c.-169G>A		5_prime_UTR_variant	1/6	1		ENSP00000221264

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6465 AN: 152172 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0337 AC: 16035 AN: 476164 Hom.: 363 Cov.: 6 AF XY: 0.0324 AC XY: 8055 AN XY: 248872

Gnomad4 AFR exome AF: 0.0725

Gnomad4 AMR exome AF: 0.0177

Gnomad4 ASJ exome AF: 0.0962

Gnomad4 EAS exome AF: 0.0000730

Gnomad4 SAS exome AF: 0.0220

Gnomad4 FIN exome AF: 0.0343

Gnomad4 NFE exome AF: 0.0344

Gnomad4 OTH exome AF: 0.0374

GnomAD4 genome AF: 0.0425 AC: 6473 AN: 152290 Hom.: 186 Cov.: 32 AF XY: 0.0414 AC XY: 3082 AN XY: 74472

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.0320

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0367 Hom.: 97

Bravo AF: 0.0440

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.6
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs4251805; hg19: chr19-44174441; COSMIC: COSV55390347; COSMIC: COSV55390347;