chr19-43647469-T-C

Variant names:

• chr19-43647469-T-C
• rs4251938
• ENST00000339082.7:c.755-921A>G

Variant summary

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

The ENST00000339082.7(PLAUR):​c.755-921A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,142 control chromosomes in the GnomAD database, including 2,148 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 0.16 (2148 hom., cov: 31)
• Consequence: PLAUR ENST00000339082.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 19 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAUR	NM_001005376.3	c.755-921A>G		intron_variant	Intron 6 of 6		NP_001005376.1
PLAUR	XM_047438925.1	c.*321-921A>G		intron_variant	Intron 7 of 7		XP_047294881.1
PLAUR	XM_017026872.3	c.*321-921A>G		intron_variant	Intron 7 of 7		XP_016882361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000339082.7	c.755-921A>G		intron_variant	Intron 6 of 6	1		ENSP00000342049.2
ENSG00000308028	ENST00000830541.1	n.91+7452T>C		intron_variant	Intron 1 of 1
ENSG00000308028	ENST00000830542.1	n.50+7387T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23793 AN: 152024 Hom.: 2144 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.157 AC: 23817 AN: 152142 Hom.: 2148 Cov.: 31 AF XY: 0.154 AC XY: 11431 AN XY: 74416

African (AFR) AF: 0.236 AC: 9779 AN: 41492

American (AMR) AF: 0.204 AC: 3120 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3466

East Asian (EAS) AF: 0.105 AC: 542 AN: 5184

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4824

European-Finnish (FIN) AF: 0.0650 AC: 690 AN: 10610

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8521 AN: 67986

Other (OTH) AF: 0.157 AC: 330 AN: 2106

Alfa AF: 0.145 Hom.: 2695

Bravo AF: 0.175

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.1
DANN	Benign	0.82
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4251938; hg19: chr19-44151621;