19-43655667-T-C

Variant names:

• chr19-43655667-T-C
• rs4251883
• NM_002659.4:c.473-94A>G

Variant summary

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

The NM_002659.4(PLAUR):​c.473-94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,118,122 control chromosomes in the GnomAD database, including 5,386 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 0.11 (1355 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4031 hom.)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002659.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	NM_002659.4	MANE Select	c.473-94A>G		intron	N/A	NP_002650.1
	PLAUR	NM_001005377.3		c.472+812A>G		intron	N/A	NP_001005377.1
	PLAUR	NM_001301037.2		c.473-94A>G		intron	N/A	NP_001287966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	ENST00000340093.8	TSL:1 MANE Select	c.473-94A>G		intron	N/A	ENSP00000339328.3
	PLAUR	ENST00000221264.8	TSL:1	c.472+812A>G		intron	N/A	ENSP00000221264.3
	PLAUR	ENST00000601723.5	TSL:1	c.473-94A>G		intron	N/A	ENSP00000471881.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16984 AN: 152174 Hom.: 1348 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0790 AC: 76328 AN: 965830 Hom.: 4031 AF XY: 0.0835 AC XY: 40415 AN XY: 484142

African (AFR) AF: 0.217 AC: 4891 AN: 22496

American (AMR) AF: 0.0585 AC: 1451 AN: 24806

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 2260 AN: 18208

East Asian (EAS) AF: 0.106 AC: 3594 AN: 33818

South Asian (SAS) AF: 0.201 AC: 12205 AN: 60852

European-Finnish (FIN) AF: 0.0361 AC: 1384 AN: 38378

Middle Eastern (MID) AF: 0.151 AC: 701 AN: 4654

European-Non Finnish (NFE) AF: 0.0637 AC: 45809 AN: 719282

Other (OTH) AF: 0.0931 AC: 4033 AN: 43336

GnomAD4 genome AF: 0.112 AC: 17027 AN: 152292 Hom.: 1355 Cov.: 32 AF XY: 0.113 AC XY: 8409 AN XY: 74480

African (AFR) AF: 0.216 AC: 8978 AN: 41534

American (AMR) AF: 0.0664 AC: 1017 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3468

East Asian (EAS) AF: 0.114 AC: 593 AN: 5184

South Asian (SAS) AF: 0.186 AC: 900 AN: 4828

European-Finnish (FIN) AF: 0.0329 AC: 350 AN: 10628

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0644 AC: 4384 AN: 68026

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.0933 Hom.: 469

Bravo AF: 0.116

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.48
PhyloP100		0.14
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: rs4251883; hg19: chr19-44159819;