chr19-43668738-A-C

Position:

• chr19-43668738-A-C

Variant summary

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

The NM_002659.4(PLAUR):​c.56-1047T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 148,486 control chromosomes in the GnomAD database, including 20,864 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 0.53 (20864 hom., cov: 25)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.56-1047T>G		intron_variant		ENST00000340093.8	NP_002650.1
LOC124904724	XR_007067264.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.56-1047T>G		intron_variant		1	NM_002659.4	ENSP00000339328	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 79072 AN: 148364 Hom.: 20839 Cov.: 25

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.537

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.533 AC: 79154 AN: 148486 Hom.: 20864 Cov.: 25 AF XY: 0.533 AC XY: 38495 AN XY: 72256

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.533

Alfa AF: 0.532 Hom.: 3743

Bravo AF: 0.523

Asia WGS AF: 0.475 AC: 1651 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs344782; hg19: chr19-44172890; COSMIC: COSV55389076; COSMIC: COSV55389076;