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: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000301.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLG	NM_000301.5	MANE Select	c.1256+9T>C		intron	N/A	NP_000292.1	P00747

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLG	ENST00000308192.14	TSL:1 MANE Select	c.1256+9T>C	intron	N/A	ENSP00000308938.9	P00747
PLG	ENST00000872438.1		c.1256+9T>C	intron	N/A	ENSP00000542497.1
PLG	ENST00000872435.1		c.1256+9T>C	intron	N/A	ENSP00000542494.1

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

10270

20540

30810

41080

51350

<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:

0.232

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.268

Hom.:

23221

Bravo

AF:

0.228

Asia WGS

AF:

0.0530

AC:

188

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over