rs4252120

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000301.5(PLG):c.1256+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,609,930 control chromosomes in the GnomAD database, including 58,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4490 hom., cov: 32)

Exomes 𝑓: 0.26 ( 54033 hom. )

Consequence

PLG
NM_000301.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.666

Publications

70 publications found

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 Gene-Disease associations (from GenCC):

hypoplasminogenemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
angioedema, hereditary, 4
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

PLG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-160722576-T-C is Benign according to our data. Variant chr6-160722576-T-C is described in ClinVar as [Benign]. Clinvar id is 1175041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLG	NM_000301.5 link	c.1256+9T>C		intron_variant	Intron 10 of 18	ENST00000308192.14	NP_000292.1	P00747

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLG	ENST00000308192.14 link	c.1256+9T>C	intron_variant	Intron 10 of 18	1	NM_000301.5	ENSP00000308938.9	P00747
PLG	ENST00000418964.2 link	c.1307+9T>C	intron_variant	Intron 10 of 18	4		ENSP00000389424.2	A6PVI2
PLG	ENST00000297289.9 link	c.209+9T>C	intron_variant	Intron 2 of 10	5		ENSP00000516619.1	A0A9L9PXP2
PLG	ENST00000706906.1 link	n.1256+9T>C	intron_variant	Intron 10 of 18			ENSP00000516618.1	A0A9L9PYG2

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35207

AN:

151918

Hom.:

4490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.246

GnomAD2 exomes

AF:

0.215

AC:

53930

AN:

251306

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.262

AC:

381619

AN:

1457894

Hom.:

54033

Cov.:

AF XY:

0.259

AC XY:

187574

AN XY:

725508

show subpopulations

African (AFR)

AF:

0.171

AC:

5710

AN:

33422

American (AMR)

AF:

0.132

AC:

5887

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

7579

AN:

26100

East Asian (EAS)

AF:

0.000529

AC:

AN:

39692

South Asian (SAS)

AF:

0.108

AC:

9289

AN:

86208

European-Finnish (FIN)

AF:

0.262

AC:

14011

AN:

53402

Middle Eastern (MID)

AF:

0.257

AC:

1464

AN:

5698

European-Non Finnish (NFE)

AF:

0.291

AC:

322750

AN:

1108396

Other (OTH)

AF:

0.247

AC:

14908

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

11969

23938

35906

47875

59844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.232

AC:

35226

AN:

152036

Hom.:

4490

Cov.:

AF XY:

0.227

AC XY:

16887

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.176

AC:

7280

AN:

41474

American (AMR)

AF:

0.203

AC:

3102

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1061

AN:

3468

East Asian (EAS)

AF:

0.00174

AC:

AN:

5178

South Asian (SAS)

AF:

0.103

AC:

496

AN:

4820

European-Finnish (FIN)

AF:

0.261

AC:

2754

AN:

10556

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19747

AN:

67950

Other (OTH)

AF:

0.244

AC:

512

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1357

2714

4072

5429

6786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.268

Hom.:

23221

Bravo

AF:

0.228

Asia WGS

AF:

0.0530

AC:

188

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

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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rs4252120

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over