chr6-160753839-C-G

Position:

• chr6-160753839-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000301.5(PLG):​c.*778C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,048 control chromosomes in the GnomAD database, including 23,181 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23181 hom., cov: 32)
• Consequence: PLG NM_000301.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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]

ENSG00000287558 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLG	NM_000301.5	c.*778C>G		3_prime_UTR_variant	19/19	ENST00000308192.14	NP_000292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14	c.*778C>G		3_prime_UTR_variant	19/19	1	NM_000301.5	ENSP00000308938.9

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82303 AN: 151930 Hom.: 23155 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.564

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.542 AC: 82375 AN: 152048 Hom.: 23181 Cov.: 32 AF XY: 0.549 AC XY: 40800 AN XY: 74290

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.569

Alfa AF: 0.402 Hom.: 1067

Bravo AF: 0.548

Asia WGS AF: 0.809 AC: 2809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11902; hg19: chr6-161174871;