chr19-43648851-C-T

Variant names:

• chr19-43648851-C-T
• rs4251923
• NM_002659.4:c.*39G>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.*39G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,587,112 control chromosomes in the GnomAD database, including 4,595 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 (1550 hom., cov: 31)
  • Exomes 𝑓: 0.050 (3045 hom.)
• Consequence: PLAUR NM_002659.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 13 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 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.*39G>A		3_prime_UTR	Exon 7 of 7	NP_002650.1
	PLAUR	NM_001005377.3		c.*39G>A		3_prime_UTR	Exon 6 of 6	NP_001005377.1
	PLAUR	NM_001301037.2		c.*39G>A		3_prime_UTR	Exon 6 of 6	NP_001287966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	ENST00000340093.8	TSL:1 MANE Select	c.*39G>A		3_prime_UTR	Exon 7 of 7	ENSP00000339328.3
	PLAUR	ENST00000221264.8	TSL:1	c.*39G>A		3_prime_UTR	Exon 6 of 6	ENSP00000221264.3
	PLAUR	ENST00000601723.5	TSL:1	c.*39G>A		3_prime_UTR	Exon 6 of 6	ENSP00000471881.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16089 AN: 152046 Hom.: 1539 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0998

GnomAD2 exomes AF: 0.0692 AC: 16619 AN: 240046 AF XY: 0.0666

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.0431

Gnomad ASJ exome AF: 0.0783

Gnomad EAS exome AF: 0.178

Gnomad FIN exome AF: 0.0299

Gnomad NFE exome AF: 0.0384

Gnomad OTH exome AF: 0.0647

GnomAD4 exome AF: 0.0497 AC: 71369 AN: 1434948 Hom.: 3045 Cov.: 30 AF XY: 0.0505 AC XY: 35810 AN XY: 709810

African (AFR) AF: 0.255 AC: 8424 AN: 33046

American (AMR) AF: 0.0464 AC: 2033 AN: 43814

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 1874 AN: 24804

East Asian (EAS) AF: 0.170 AC: 6688 AN: 39258

South Asian (SAS) AF: 0.0736 AC: 6162 AN: 83708

European-Finnish (FIN) AF: 0.0311 AC: 1639 AN: 52684

Middle Eastern (MID) AF: 0.129 AC: 566 AN: 4400

European-Non Finnish (NFE) AF: 0.0365 AC: 39983 AN: 1094162

Other (OTH) AF: 0.0677 AC: 4000 AN: 59072

GnomAD4 genome AF: 0.106 AC: 16140 AN: 152164 Hom.: 1550 Cov.: 31 AF XY: 0.105 AC XY: 7834 AN XY: 74402

African (AFR) AF: 0.250 AC: 10377 AN: 41476

American (AMR) AF: 0.0681 AC: 1041 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3472

East Asian (EAS) AF: 0.174 AC: 897 AN: 5164

South Asian (SAS) AF: 0.0704 AC: 340 AN: 4830

European-Finnish (FIN) AF: 0.0299 AC: 317 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0383 AC: 2603 AN: 68000

Other (OTH) AF: 0.100 AC: 212 AN: 2116

Alfa AF: 0.0535 Hom.: 139

Bravo AF: 0.116

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.31
DANN	Benign	0.66
PhyloP100		-1.3
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: rs4251923; hg19: chr19-44153003; COSMIC: COSV55390474; COSMIC: COSV55390474;