rs4252109

Positions:

chr6-160716631-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000301.5(PLG):c.669-14T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,419,248 control chromosomes in the GnomAD database, including 50,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4409 hom., cov: 32)

Exomes 𝑓: 0.26 ( 45960 hom. )

Consequence

PLG
NM_000301.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.993

Variant links:

Genes affected

PLG (HGNC:9071): (plasminogen) The plasminogen protein encoded by this gene is a serine protease that circulates in blood plasma as an inactive zymogen and is converted to the active protease, plasmin, by several plasminogen activators such as tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), kallikrein, and factor XII (Hageman factor). The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-561 and Val-562. Plasmin cleavage also releases the angiostatin protein which inhibits angiogenesis. Plasmin degrades many blood plasma proteins, including fibrin-containing blood clots. As a serine protease, plasmin cleaves many products in addition to fibrin such as fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin is inactivated by proteins such as alpha-2-macroglobulin and alpha-2-antiplasmin in addition to inhibitors of the various plasminogen activators. Plasminogen also interacts with plasminogen receptors which results in the retention of plasmin on cell surfaces and in plasmin-induced cell signaling. The localization of plasminogen on cell surfaces plays a role in the degradation of extracellular matrices, cell migration, inflamation, wound healing, oncogenesis, metastasis, myogenesis, muscle regeneration, neurite outgrowth, and fibrinolysis. This protein may also play a role in acute respiratory distress syndrome (ARDS) which, in part, is caused by enhanced clot formation and the suppression of fibrinolysis. Compared to other mammals, the cluster of plasminogen-like genes to which this gene belongs has been rearranged in catarrhine primates. [provided by RefSeq, May 2020]

PLG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-160716631-T-G is Benign according to our data. Variant chr6-160716631-T-G is described in ClinVar as [Benign]. Clinvar id is 1175104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-160716631-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLG	NM_000301.5 linkuse as main transcript	c.669-14T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000308192.14	NP_000292.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
PLG	ENST00000308192.14 linkuse as main transcript	c.669-14T>G	splice_polypyrimidine_tract_variant, intron_variant	1	NM_000301.5	ENSP00000308938	P1
PLG	ENST00000297289.9 linkuse as main transcript	c.50-5777T>G	intron_variant	5		ENSP00000516619
PLG	ENST00000418964.2 linkuse as main transcript	c.720-14T>G	splice_polypyrimidine_tract_variant, intron_variant	4		ENSP00000389424
PLG	ENST00000706906.1 linkuse as main transcript	c.669-14T>G	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant			ENSP00000516618

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34800

AN:

152010

Hom.:

4412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.214

AC:

53652

AN:

251030

Hom.:

7025

AF XY:

0.216

AC XY:

29353

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.000708

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.258

AC:

327187

AN:

1267120

Hom.:

45960

Cov.:

AF XY:

0.255

AC XY:

163607

AN XY:

641296

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.131

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.000515

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.291

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.229

AC:

34806

AN:

152128

Hom.:

4409

Cov.:

AF XY:

0.224

AC XY:

16658

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.260

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.277

Hom.:

6586

Bravo

AF:

0.225

Asia WGS

AF:

0.0550

AC:

194

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.63

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over