Variant 6-160702381-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000301.5(PLG):c.49+28G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,447,266 control chromosomes in the GnomAD database, including 135,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 14563 hom., cov: 32)

Exomes 𝑓: 0.43 ( 120982 hom. )

Consequence

PLG
NM_000301.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.152

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=-0.92).

BP6

Variant 6-160702381-G-T is Benign according to our data. Variant chr6-160702381-G-T is described in ClinVar as [Benign]. Clinvar id is 1252883.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 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.49+28G>T		intron_variant		ENST00000308192.14	NP_000292.1
PLG	NM_001168338.1 linkuse as main transcript	c.49+28G>T		intron_variant			NP_001161810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14 linkuse as main transcript	c.49+28G>T		intron_variant		1	NM_000301.5	ENSP00000308938	P1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65812

AN:

151828

Hom.:

14555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.448

GnomAD3 exomes

AF:

0.397

AC:

63888

AN:

161030

Hom.:

13599

AF XY:

0.401

AC XY:

35464

AN XY:

88386

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.426

AC:

551933

AN:

1295320

Hom.:

120982

Cov.:

AF XY:

0.428

AC XY:

278082

AN XY:

650350

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.473

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.367

Gnomad4 FIN exome

AF:

0.487

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.433

AC:

65844

AN:

151946

Hom.:

14563

Cov.:

AF XY:

0.429

AC XY:

31834

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.355

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.384

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.476

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.451

Hom.:

2122

Bravo

AF:

0.423

Asia WGS

AF:

0.298

AC:

1040

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.76

DANN

Benign

0.26

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

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