chr19-43670289-C-T

Variant names:

• chr19-43670289-C-T
• rs4251805
• ENST00000221264.8:c.-169G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.72).
• 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 rank	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.-169G>A		upstream_gene_variant		ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.-169G>A		upstream_gene_variant		1	NM_002659.4	ENSP00000339328.3

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

African (AFR) AF: 0.0725 AC: 824 AN: 11362

American (AMR) AF: 0.0177 AC: 279 AN: 15754

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 1291 AN: 13422

East Asian (EAS) AF: 0.0000730 AC: 2 AN: 27388

South Asian (SAS) AF: 0.0220 AC: 983 AN: 44678

European-Finnish (FIN) AF: 0.0343 AC: 1003 AN: 29248

Middle Eastern (MID) AF: 0.0649 AC: 130 AN: 2002

European-Non Finnish (NFE) AF: 0.0344 AC: 10529 AN: 305718

Other (OTH) AF: 0.0374 AC: 994 AN: 26592

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

African (AFR) AF: 0.0694 AC: 2885 AN: 41564

American (AMR) AF: 0.0204 AC: 312 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 290 AN: 3462

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4832

European-Finnish (FIN) AF: 0.0320 AC: 340 AN: 10612

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2409 AN: 68026

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0368 Hom.: 114

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
PhyloP100		0.85
PromoterAI		-0.094	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4251805; hg19: chr19-44174441; COSMIC: COSV55390347; COSMIC: COSV55390347;