10-73909561-C-T

Variant summary

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

The ENST00000481390.5(PLAU):c.-32+267C>T 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 152,092 control chromosomes in the GnomAD database, including 40,711 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 0.73 (40711 hom., cov: 32)
• Consequence: PLAU ENST00000481390.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

Genes affected

PLAU (HGNC:9052): (plasminogen activator, urokinase) This gene encodes a secreted serine protease that converts plasminogen to plasmin. The encoded preproprotein is proteolytically processed to generate A and B polypeptide chains. These chains associate via a single disulfide bond to form the catalytically inactive high molecular weight urokinase-type plasminogen activator (HMW-uPA). HMW-uPA can be further processed into the catalytically active low molecular weight urokinase-type plasminogen activator (LMW-uPA). This low molecular weight form does not bind to the urokinase-type plasminogen activator receptor. Mutations in this gene may be associated with Quebec platelet disorder and late-onset Alzheimer's disease. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAU	XM_011539866.3	c.-32+267C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAU	ENST00000481390.5	c.-32+267C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110242 AN: 151974 Hom.: 40676 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.766

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.725 AC: 110318 AN: 152092 Hom.: 40711 Cov.: 32 AF XY: 0.715 AC XY: 53161 AN XY: 74316

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.757

Alfa AF: 0.744 Hom.: 70642

Bravo AF: 0.729

Asia WGS AF: 0.526 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.5
Dann	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2227552; hg19: chr10-75669319;