rs4251831

Variant names:

• chr19-43665586-G-A
• rs4251831
• NM_002659.4:c.167-127C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43665586-G-A
• chr19-43665586-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002659.4(PLAUR):​c.167-127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000614 in 813,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000069 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: PLAUR NM_002659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.167-127C>T		intron	N/A	NP_002650.1	Q03405-1
	PLAUR	NM_001005377.3		c.167-127C>T		intron	N/A	NP_001005377.1	Q03405-3
	PLAUR	NM_001301037.2		c.167-127C>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.167-127C>T		intron	N/A	ENSP00000339328.3	Q03405-1
	PLAUR	ENST00000221264.8	TSL:1	c.167-127C>T		intron	N/A	ENSP00000221264.3	Q03405-3
	PLAUR	ENST00000601723.5	TSL:1	c.167-127C>T		intron	N/A	ENSP00000471881.1	M0R1I2

Frequencies

GnomAD3 genomes AF: 0.00000687 AC: 1 AN: 145582 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000599 AC: 4 AN: 668152 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 340996

African (AFR) AF: 0.00 AC: 0 AN: 17310

American (AMR) AF: 0.00 AC: 0 AN: 23484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14932

East Asian (EAS) AF: 0.00 AC: 0 AN: 32484

South Asian (SAS) AF: 0.00 AC: 0 AN: 46234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2328

European-Non Finnish (NFE) AF: 0.00000860 AC: 4 AN: 465086

Other (OTH) AF: 0.00 AC: 0 AN: 32362

GnomAD4 genome AF: 0.00000687 AC: 1 AN: 145582 Hom.: 0 Cov.: 19 AF XY: 0.0000142 AC XY: 1 AN XY: 70448

African (AFR) AF: 0.00 AC: 0 AN: 38950

American (AMR) AF: 0.00 AC: 0 AN: 14150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4856

South Asian (SAS) AF: 0.00 AC: 0 AN: 4398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66828

Other (OTH) AF: 0.00 AC: 0 AN: 1958

Alfa AF: 0.000106 Hom.: 5101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.91
PhyloP100		-0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4251831;

hg19: chr19-44169738;