rs2295368

Positions:

chr6-160718470-G-A

Variant summary

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

The NM_000301.5(PLG):c.950+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,589,508 control chromosomes in the GnomAD database, including 125,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10053 hom., cov: 32)

Exomes 𝑓: 0.40 ( 115062 hom. )

Consequence

PLG
NM_000301.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.79

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=-0.78).

BP6

Variant 6-160718470-G-A is Benign according to our data. Variant chr6-160718470-G-A is described in ClinVar as [Benign]. Clinvar id is 1174642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-160718470-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLG	NM_000301.5 linkuse as main transcript	c.950+14G>A		intron_variant		ENST00000308192.14

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
PLG	ENST00000308192.14 linkuse as main transcript	c.950+14G>A	intron_variant	1	NM_000301.5	P1
PLG	ENST00000297289.9 linkuse as main transcript	c.50-3938G>A	intron_variant	5
PLG	ENST00000418964.2 linkuse as main transcript	c.1001+14G>A	intron_variant	4
PLG	ENST00000706906.1 linkuse as main transcript	c.950+14G>A	intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54068

AN:

151868

Hom.:

10051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.374

AC:

94054

AN:

251162

Hom.:

18245

AF XY:

0.382

AC XY:

51893

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.411

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.409

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.397

AC:

570281

AN:

1437522

Hom.:

115062

Cov.:

AF XY:

0.399

AC XY:

286083

AN XY:

716920

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.280

Gnomad4 ASJ exome

AF:

0.411

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.411

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.392

GnomAD4 genome

AF:

0.356

AC:

54084

AN:

151986

Hom.:

10053

Cov.:

AF XY:

0.355

AC XY:

26374

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.418

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.400

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.394

Hom.:

13720

Bravo

AF:

0.348

Asia WGS

AF:

0.382

AC:

1329

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Angioedema, hereditary, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Plasminogen deficiency, type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.11

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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