chr6-160716747-T-C

Position:

chr6-160716747-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000301.5(PLG):c.771T>C(p.Cys257Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,600,012 control chromosomes in the GnomAD database, including 145,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15487 hom., cov: 32)

Exomes 𝑓: 0.42 ( 130413 hom. )

Consequence

PLG
NM_000301.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.334

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-160716747-T-C is Benign according to our data. Variant chr6-160716747-T-C is described in ClinVar as [Benign]. Clinvar id is 1175116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-160716747-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.334 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLG	NM_000301.5 linkuse as main transcript	c.771T>C	p.Cys257Cys	synonymous_variant	7/19	ENST00000308192.14	NP_000292.1	P00747

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLG	ENST00000308192.14 linkuse as main transcript	c.771T>C	p.Cys257Cys	synonymous_variant	7/19	1	NM_000301.5	ENSP00000308938.9	P00747
PLG	ENST00000418964.2 linkuse as main transcript	c.822T>C	p.Cys274Cys	synonymous_variant	7/19	4		ENSP00000389424.2	A6PVI2
PLG	ENST00000297289.9 linkuse as main transcript	c.50-5661T>C		intron_variant		5		ENSP00000516619.1	A0A9L9PXP2
PLG	ENST00000706906.1 linkuse as main transcript	n.771T>C		non_coding_transcript_exon_variant	7/19			ENSP00000516618.1	A0A9L9PYG2

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67863

AN:

151930

Hom.:

15484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.505

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.451

GnomAD3 exomes

AF:

0.414

AC:

104031

AN:

251182

Hom.:

22167

AF XY:

0.418

AC XY:

56789

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.491

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.422

AC:

610359

AN:

1447964

Hom.:

130413

Cov.:

AF XY:

0.424

AC XY:

305521

AN XY:

721148

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.318

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.456

Gnomad4 FIN exome

AF:

0.346

Gnomad4 NFE exome

AF:

0.420

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.447

AC:

67907

AN:

152048

Hom.:

15487

Cov.:

AF XY:

0.443

AC XY:

32894

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.530

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.496

Gnomad4 EAS

AF:

0.455

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.424

Gnomad4 OTH

AF:

0.449

Alfa

AF:

0.428

Hom.:

25484

Bravo

AF:

0.450

Asia WGS

AF:

0.420

AC:

1459

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Angioedema, hereditary, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Plasminogen deficiency, type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.59

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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