chr6-160718470-G-A

Variant names:

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.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

Publications

15 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 6-160718470-G-A is Benign according to our data. Variant chr6-160718470-G-A is described in ClinVar as Benign. ClinVar VariationId is 1174642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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.950+14G>A		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.950+14G>A	intron	N/A	ENSP00000308938.9	P00747
PLG	ENST00000872438.1		c.950+14G>A	intron	N/A	ENSP00000542497.1
PLG	ENST00000872435.1		c.950+14G>A	intron	N/A	ENSP00000542494.1

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

GnomAD2 exomes

AF:

0.374

AC:

94054

AN:

251162

AF XY:

0.382

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 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

African (AFR)

AF:

0.245

AC:

8115

AN:

33124

American (AMR)

AF:

0.280

AC:

12519

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

10661

AN:

25966

East Asian (EAS)

AF:

0.439

AC:

17378

AN:

39574

South Asian (SAS)

AF:

0.411

AC:

35218

AN:

85766

European-Finnish (FIN)

AF:

0.343

AC:

18306

AN:

53404

Middle Eastern (MID)

AF:

0.319

AC:

1827

AN:

5730

European-Non Finnish (NFE)

AF:

0.406

AC:

442900

AN:

1089630

Other (OTH)

AF:

0.392

AC:

23357

AN:

59626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

15941

31881

47822

63762

79703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13492

26984

40476

53968

67460

<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:

0.356

AC:

54084

AN:

151986

Hom.:

10053

Cov.:

AF XY:

0.355

AC XY:

26374

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.258

AC:

10681

AN:

41434

American (AMR)

AF:

0.318

AC:

4864

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1450

AN:

3472

East Asian (EAS)

AF:

0.453

AC:

2338

AN:

5156

South Asian (SAS)

AF:

0.400

AC:

1929

AN:

4820

European-Finnish (FIN)

AF:

0.339

AC:

3570

AN:

10540

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27950

AN:

67968

Other (OTH)

AF:

0.355

AC:

751

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1795

3589

5384

7178

8973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.391

Hom.:

19471

Bravo

AF:

0.348

Asia WGS

AF:

0.382

AC:

1329

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)

Angioedema, hereditary, 4 (1)

Plasminogen deficiency, type I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.11

(source)

DANN

Benign

0.85

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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