NM_000301.5:c.49+28G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000301.5(PLG):c.49+28G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,447,266 control chromosomes in the GnomAD database, including 135,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 14563 hom., cov: 32)

Exomes 𝑓: 0.43 ( 120982 hom. )

Consequence

PLG
NM_000301.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.152

Publications

6 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-160702381-G-T is Benign according to our data. Variant chr6-160702381-G-T is described in ClinVar as [Benign]. Clinvar id is 1252883.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLG	NM_000301.5 link	c.49+28G>T		intron_variant	Intron 1 of 18	ENST00000308192.14	NP_000292.1	P00747
PLG	NM_001168338.1 link	c.49+28G>T		intron_variant	Intron 1 of 3		NP_001161810.1	Q5TEH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14 link	c.49+28G>T		intron_variant	Intron 1 of 18	1	NM_000301.5	ENSP00000308938.9		P00747

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65812

AN:

151828

Hom.:

14555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.448

GnomAD2 exomes

AF:

0.397

AC:

63888

AN:

161030

AF XY:

0.401

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.426

AC:

551933

AN:

1295320

Hom.:

120982

Cov.:

AF XY:

0.428

AC XY:

278082

AN XY:

650350

show subpopulations

African (AFR)

AF:

0.370

AC:

10764

AN:

29094

American (AMR)

AF:

0.248

AC:

10158

AN:

40992

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

11431

AN:

24178

East Asian (EAS)

AF:

0.164

AC:

6340

AN:

38556

South Asian (SAS)

AF:

0.367

AC:

28609

AN:

77896

European-Finnish (FIN)

AF:

0.487

AC:

24648

AN:

50594

Middle Eastern (MID)

AF:

0.430

AC:

1609

AN:

3740

European-Non Finnish (NFE)

AF:

0.446

AC:

435539

AN:

975856

Other (OTH)

AF:

0.420

AC:

22835

AN:

54414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

12204

24408

36613

48817

61021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.433

AC:

65844

AN:

151946

Hom.:

14563

Cov.:

AF XY:

0.429

AC XY:

31834

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.407

AC:

16855

AN:

41446

American (AMR)

AF:

0.355

AC:

5425

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1733

AN:

3464

East Asian (EAS)

AF:

0.181

AC:

936

AN:

5166

South Asian (SAS)

AF:

0.384

AC:

1847

AN:

4816

European-Finnish (FIN)

AF:

0.495

AC:

5210

AN:

10528

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32358

AN:

67944

Other (OTH)

AF:

0.444

AC:

936

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1889

3777

5666

7554

9443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.451

Hom.:

2122

Bravo

AF:

0.423

Asia WGS

AF:

0.298

AC:

1040

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

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

-0.92

CADD

Benign

0.76

(source)

DANN

Benign

0.26

PhyloP100

0.15

PromoterAI

-0.0055

Neutral

(source)

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

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

NM_000301.5:c.49+28G>T

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