chr6-160702419-T-C

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+66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 1,389,948 control chromosomes in the GnomAD database, including 4,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.056 ( 351 hom., cov: 33)

Exomes 𝑓: 0.078 ( 4532 hom. )

Consequence

PLG
NM_000301.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.165

Publications

28 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=-0.91).

BP6

Variant 6-160702419-T-C is Benign according to our data. Variant chr6-160702419-T-C is described in ClinVar as [Benign]. Clinvar id is 1221071.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLG	NM_000301.5 link	c.49+66T>C		intron_variant	Intron 1 of 18	ENST00000308192.14	NP_000292.1	P00747
PLG	NM_001168338.1 link	c.49+66T>C		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+66T>C		intron_variant	Intron 1 of 18	1	NM_000301.5	ENSP00000308938.9		P00747

Frequencies

GnomAD3 genomes

AF:

0.0562

AC:

8556

AN:

152190

Hom.:

351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0475

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00912

Gnomad FIN

AF:

0.0507

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0895

Gnomad OTH

AF:

0.0501

GnomAD4 exome

AF:

0.0775

AC:

95937

AN:

1237640

Hom.:

4532

AF XY:

0.0753

AC XY:

46982

AN XY:

623690

show subpopulations

African (AFR)

AF:

0.0180

AC:

493

AN:

27422

American (AMR)

AF:

0.0314

AC:

1239

AN:

39462

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

652

AN:

23812

East Asian (EAS)

AF:

0.000583

AC:

AN:

37764

South Asian (SAS)

AF:

0.0116

AC:

878

AN:

75484

European-Finnish (FIN)

AF:

0.0597

AC:

2985

AN:

50034

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

3624

European-Non Finnish (NFE)

AF:

0.0931

AC:

86318

AN:

927484

Other (OTH)

AF:

0.0626

AC:

3288

AN:

52554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

3759

7518

11276

15035

18794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0562

AC:

8555

AN:

152308

Hom.:

351

Cov.:

AF XY:

0.0519

AC XY:

3868

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0218

AC:

907

AN:

41580

American (AMR)

AF:

0.0473

AC:

724

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

108

AN:

3468

East Asian (EAS)

AF:

0.00212

AC:

AN:

5186

South Asian (SAS)

AF:

0.00892

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0507

AC:

538

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0895

AC:

6090

AN:

68024

Other (OTH)

AF:

0.0496

AC:

105

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

430

859

1289

1718

2148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0685

Hom.:

Bravo

AF:

0.0541

Asia WGS

AF:

0.00982

AC:

AN:

3478

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

-0.91

CADD

Benign

0.73

(source)

DANN

Benign

0.78

PhyloP100

-0.17

PromoterAI

0.0098

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.

chr6-160702419-T-C

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