rs4252125

Positions:

chr6-160731208-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000301.5(PLG):c.1414G>A(p.Asp472Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,613,350 control chromosomes in the GnomAD database, including 58,614 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4498 hom., cov: 32)

Exomes 𝑓: 0.26 ( 54116 hom. )

Consequence

PLG
NM_000301.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0650

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042169094).

BP6

Variant 6-160731208-G-A is Benign according to our data. Variant chr6-160731208-G-A is described in ClinVar as [Benign]. Clinvar id is 692202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-160731208-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLG	NM_000301.5 link	c.1414G>A	p.Asp472Asn	missense_variant	11/19	ENST00000308192.14	NP_000292.1	P00747

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14 link	c.1414G>A	p.Asp472Asn	missense_variant	11/19	1	NM_000301.5	ENSP00000308938.9		P00747

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35235

AN:

152058

Hom.:

4498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.215

AC:

53916

AN:

251298

Hom.:

7125

AF XY:

0.217

AC XY:

29422

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.262

AC:

383007

AN:

1461174

Hom.:

54116

Cov.:

AF XY:

0.259

AC XY:

188134

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.232

AC:

35254

AN:

152176

Hom.:

4498

Cov.:

AF XY:

0.227

AC XY:

16909

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.290

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.272

Hom.:

10402

Bravo

AF:

0.228

TwinsUK

AF:

0.304

AC:

1127

ALSPAC

AF:

0.288

AC:

1110

ESP6500AA

AF:

0.182

AC:

804

ESP6500EA

AF:

0.303

AC:

2604

ExAC

AF:

0.217

AC:

26356

Asia WGS

AF:

0.0540

AC:

190

AN:

3478

EpiCase

AF:

0.297

EpiControl

AF:

0.308

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 18566672, 15269832) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Otitis media, susceptibility to

Benign:1

Benign, no assertion criteria provided

research

Santos-Cortez Lab, University of Colorado School of Medicine

Jul 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.88

DANN

Benign

0.66

DEOGEN2

Benign

0.11

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.96

PrimateAI

Benign

0.26

PROVEAN

Benign

0.33

REVEL

Benign

0.063

Sift

Benign

0.40

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.014

MPC

0.20

ClinPred

0.0014

GERP RS

2.1

Varity_R

0.032

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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