rs344781

Variant names:

• chr19-43670636-C-T
• rs344781
• ENST00000830545.1:n.189+156C>T

Variant summary

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

The ENST00000830545.1(ENSG00000308028):​n.189+156C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 153,918 control chromosomes in the GnomAD database, including 49,489 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 0.80 (48952 hom., cov: 30)
  • Exomes 𝑓: 0.76 (537 hom.)
• Consequence: ENSG00000308028 ENST00000830545.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 35 publications found

Genes affected

ENSG00000308028 (HGNC:):

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]

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 = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124904724	XR_007067264.1	n.875+156C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000308028	ENST00000830545.1	n.189+156C>T		intron_variant	Intron 1 of 1
ENSG00000308028	ENST00000830546.1	n.165+156C>T		intron_variant	Intron 1 of 1
PLAUR	ENST00000221264.8	c.-516G>A		upstream_gene_variant		1		ENSP00000221264.3

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121129 AN: 151944 Hom.: 48900 Cov.: 30

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.800

GnomAD4 exome AF: 0.755 AC: 1402 AN: 1856 Hom.: 537 AF XY: 0.756 AC XY: 800 AN XY: 1058

African (AFR) AF: 0.950 AC: 57 AN: 60

American (AMR) AF: 0.719 AC: 23 AN: 32

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 39 AN: 48

East Asian (EAS) AF: 0.636 AC: 28 AN: 44

South Asian (SAS) AF: 0.701 AC: 289 AN: 412

European-Finnish (FIN) AF: 0.797 AC: 51 AN: 64

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.766 AC: 835 AN: 1090

Other (OTH) AF: 0.755 AC: 77 AN: 102

GnomAD4 genome AF: 0.797 AC: 121242 AN: 152062 Hom.: 48952 Cov.: 30 AF XY: 0.790 AC XY: 58701 AN XY: 74326

African (AFR) AF: 0.926 AC: 38444 AN: 41502

American (AMR) AF: 0.748 AC: 11420 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2753 AN: 3472

East Asian (EAS) AF: 0.542 AC: 2797 AN: 5158

South Asian (SAS) AF: 0.665 AC: 3208 AN: 4822

European-Finnish (FIN) AF: 0.724 AC: 7630 AN: 10540

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52382 AN: 67992

Other (OTH) AF: 0.800 AC: 1689 AN: 2112

Alfa AF: 0.772 Hom.: 37902

Bravo AF: 0.803

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.83
PhyloP100		-0.41
PromoterAI		0.092	Neutral
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: rs344781; hg19: chr19-44174788;