Genetic Variant PLG:c.-152T>C (chr6-160702153-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000301.5(PLG):c.-152T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 802,580 control chromosomes in the GnomAD database, including 106,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 19408 hom., cov: 31)

Exomes 𝑓: 0.50 ( 86823 hom. )

Consequence

PLG
NM_000301.5 upstream_gene

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.98

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 6-160702153-T-C is Benign according to our data. Variant chr6-160702153-T-C is described in ClinVar as [Benign]. Clinvar id is 1230328.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLG	NM_000301.5 link	c.-152T>C		upstream_gene_variant		ENST00000308192.14	NP_000292.1	P00747
PLG	NM_001168338.1 link	c.-152T>C		upstream_gene_variant			NP_001161810.1	Q5TEH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14 link	c.-152T>C		upstream_gene_variant		1	NM_000301.5	ENSP00000308938.9		P00747

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75178

AN:

151794

Hom.:

19400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.574

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.498

GnomAD4 exome

AF:

0.502

AC:

326353

AN:

650668

Hom.:

86823

AF XY:

0.500

AC XY:

175108

AN XY:

350408

show subpopulations

Gnomad4 AFR exome

AF:

0.403

Gnomad4 AMR exome

AF:

0.309

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.576

Gnomad4 NFE exome

AF:

0.557

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.495

AC:

75216

AN:

151912

Hom.:

19408

Cov.:

AF XY:

0.488

AC XY:

36239

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.398

Gnomad4 ASJ

AF:

0.555

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.574

Gnomad4 NFE

AF:

0.577

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.515

Hom.:

3217

Bravo

AF:

0.478

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

-0.67

CADD

Benign

DANN

Benign

0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over