rs4252170

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000301.5(PLG):c.2082T>C(p.Ala694Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 1,612,254 control chromosomes in the GnomAD database, including 5,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 385 hom., cov: 33)

Exomes 𝑓: 0.078 ( 4836 hom. )

Consequence

PLG
NM_000301.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.02

Publications

14 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-160741374-T-C is Benign according to our data. Variant chr6-160741374-T-C is described in ClinVar as Benign. ClinVar VariationId is 1268733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLG	NM_000301.5 link	c.2082T>C	p.Ala694Ala	synonymous_variant	Exon 17 of 19	ENST00000308192.14	NP_000292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14 link	c.2082T>C	p.Ala694Ala	synonymous_variant	Exon 17 of 19	1	NM_000301.5	ENSP00000308938.9

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9653

AN:

152240

Hom.:

382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0651

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.0976

Gnomad SAS

AF:

0.0553

Gnomad FIN

AF:

0.0989

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0815

Gnomad OTH

AF:

0.0798

GnomAD2 exomes

AF:

0.0740

AC:

18616

AN:

251476

AF XY:

0.0742

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.0554

Gnomad ASJ exome

AF:

0.0886

Gnomad EAS exome

AF:

0.0969

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0824

Gnomad OTH exome

AF:

0.0902

GnomAD4 exome

AF:

0.0785

AC:

114579

AN:

1459896

Hom.:

4836

Cov.:

AF XY:

0.0775

AC XY:

56265

AN XY:

726420

show subpopulations

African (AFR)

AF:

0.0184

AC:

616

AN:

33462

American (AMR)

AF:

0.0577

AC:

2582

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0863

AC:

2254

AN:

26120

East Asian (EAS)

AF:

0.113

AC:

4482

AN:

39676

South Asian (SAS)

AF:

0.0517

AC:

4455

AN:

86238

European-Finnish (FIN)

AF:

0.0982

AC:

5243

AN:

53412

Middle Eastern (MID)

AF:

0.0970

AC:

559

AN:

5760

European-Non Finnish (NFE)

AF:

0.0805

AC:

89414

AN:

1110186

Other (OTH)

AF:

0.0825

AC:

4974

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

4851

9702

14554

19405

24256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3236

6472

9708

12944

16180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0634

AC:

9659

AN:

152358

Hom.:

385

Cov.:

AF XY:

0.0638

AC XY:

4753

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0185

AC:

769

AN:

41602

American (AMR)

AF:

0.0651

AC:

996

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

268

AN:

3472

East Asian (EAS)

AF:

0.0975

AC:

505

AN:

5182

South Asian (SAS)

AF:

0.0547

AC:

264

AN:

4824

European-Finnish (FIN)

AF:

0.0989

AC:

1050

AN:

10616

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0815

AC:

5547

AN:

68032

Other (OTH)

AF:

0.0855

AC:

181

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

477

954

1431

1908

2385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0772

Hom.:

1696

Bravo

AF:

0.0592

Asia WGS

AF:

0.128

AC:

446

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 09, 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

-0.89

CADD

Benign

0.098

(source)

DANN

Benign

0.69

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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