NM_002659.4:c.311-2989T>A

Variant names:

• chr19-43659629-A-T
• rs397374
• NM_002659.4:c.311-2989T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002659.4(PLAUR):​c.311-2989T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,036 control chromosomes in the GnomAD database, including 6,441 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 0.28 (6441 hom., cov: 32)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 4 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.311-2989T>A		intron_variant	Intron 3 of 6	ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.311-2989T>A		intron_variant	Intron 3 of 6	1	NM_002659.4	ENSP00000339328.3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42066 AN: 151918 Hom.: 6435 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.277 AC: 42090 AN: 152036 Hom.: 6441 Cov.: 32 AF XY: 0.279 AC XY: 20716 AN XY: 74334

African (AFR) AF: 0.290 AC: 12013 AN: 41430

American (AMR) AF: 0.372 AC: 5683 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3472

East Asian (EAS) AF: 0.667 AC: 3446 AN: 5164

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4824

European-Finnish (FIN) AF: 0.228 AC: 2411 AN: 10584

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15831 AN: 67972

Other (OTH) AF: 0.280 AC: 590 AN: 2110

Alfa AF: 0.247 Hom.: 678

Bravo AF: 0.290

Asia WGS AF: 0.426 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.95
PhyloP100		1.0
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

Other links and lift over

dbSNP: rs397374; hg19: chr19-44163781;