Variant chr6-160702419-T-C 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+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

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=-0.91).

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/exons	MANE	UniProt
PLG	NM_000301.5 linkuse as main transcript	c.49+66T>C		intron_variant		ENST00000308192.14
PLG	NM_001168338.1 linkuse as main transcript	c.49+66T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLG	ENST00000308192.14 linkuse as main transcript	c.49+66T>C		intron_variant		1	NM_000301.5	P1

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

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.0314

Gnomad4 ASJ exome

AF:

0.0274

Gnomad4 EAS exome

AF:

0.000583

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.0597

Gnomad4 NFE exome

AF:

0.0931

Gnomad4 OTH exome

AF:

0.0626

GnomAD4 genome

AF:

0.0562

AC:

8555

AN:

152308

Hom.:

351

Cov.:

AF XY:

0.0519

AC XY:

3868

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.0473

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.00892

Gnomad4 FIN

AF:

0.0507

Gnomad4 NFE

AF:

0.0895

Gnomad4 OTH

AF:

0.0496

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

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

-0.91

CADD

Benign

0.73

DANN

Benign

0.78

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