rs4251846

Variant names:

• chr19-43661302-G-A
• rs4251846
• NM_002659.4:c.310+4014C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43661302-G-A
• chr19-43661302-G-C
• chr19-43661302-G-T

Variant summary

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

The NM_002659.4(PLAUR):​c.310+4014C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,140 control chromosomes in the GnomAD database, including 1,067 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 (1067 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	NM_002659.4	MANE Select	c.310+4014C>T		intron	N/A	NP_002650.1	Q03405-1
	PLAUR	NM_001005377.3		c.310+4014C>T		intron	N/A	NP_001005377.1	Q03405-3
	PLAUR	NM_001301037.2		c.310+4014C>T		intron	N/A	NP_001287966.1	M0R1I2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	ENST00000340093.8	TSL:1 MANE Select	c.310+4014C>T		intron	N/A	ENSP00000339328.3	Q03405-1
	PLAUR	ENST00000221264.8	TSL:1	c.310+4014C>T		intron	N/A	ENSP00000221264.3	Q03405-3
	PLAUR	ENST00000601723.5	TSL:1	c.310+4014C>T		intron	N/A	ENSP00000471881.1	M0R1I2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17364 AN: 152022 Hom.: 1066 Cov.: 31

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0760

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.0986

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.114 AC: 17368 AN: 152140 Hom.: 1067 Cov.: 31 AF XY: 0.113 AC XY: 8415 AN XY: 74374

African (AFR) AF: 0.0813 AC: 3375 AN: 41522

American (AMR) AF: 0.138 AC: 2107 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0760 AC: 264 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1178 AN: 5174

South Asian (SAS) AF: 0.0895 AC: 431 AN: 4816

European-Finnish (FIN) AF: 0.0986 AC: 1042 AN: 10568

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8621 AN: 68004

Other (OTH) AF: 0.111 AC: 235 AN: 2114

Alfa AF: 0.0785 Hom.: 124

Bravo AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		0.028
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: rs4251846; hg19: chr19-44165454;