Variant 6-160702270-G-A 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.-35G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00755 in 1,608,996 control chromosomes in the GnomAD database, including 355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 165 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 190 hom. )

Consequence

PLG
NM_000301.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.92

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=-0.81).

BP6

Variant 6-160702270-G-A is Benign according to our data. Variant chr6-160702270-G-A is described in ClinVar as [Benign]. Clinvar id is 1248531.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0829 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.-35G>A		5_prime_UTR_variant	1/19	ENST00000308192.14
PLG	NM_001168338.1 linkuse as main transcript	c.-35G>A		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLG	ENST00000308192.14 linkuse as main transcript	c.-35G>A		5_prime_UTR_variant	1/19	1	NM_000301.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4247

AN:

152170

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0854

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.00342

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0109

AC:

2529

AN:

231250

Hom.:

AF XY:

0.00898

AC XY:

1126

AN XY:

125406

show subpopulations

Gnomad AFR exome

AF:

0.0910

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.0274

Gnomad EAS exome

AF:

0.000408

Gnomad SAS exome

AF:

0.00159

Gnomad FIN exome

AF:

0.0000547

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.00542

AC:

7902

AN:

1456708

Hom.:

190

Cov.:

AF XY:

0.00519

AC XY:

3763

AN XY:

724686

show subpopulations

Gnomad4 AFR exome

AF:

0.0876

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0293

Gnomad4 EAS exome

AF:

0.00212

Gnomad4 SAS exome

AF:

0.00205

Gnomad4 FIN exome

AF:

0.0000388

Gnomad4 NFE exome

AF:

0.00221

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.0279

AC:

4251

AN:

152288

Hom.:

165

Cov.:

AF XY:

0.0263

AC XY:

1955

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0853

Gnomad4 AMR

AF:

0.0186

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.00774

Hom.:

Bravo

AF:

0.0326

Asia WGS

AF:

0.00636

AC:

AN:

3476

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

Jun 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.73

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