NM_000301.5:c.*778C>G

Variant names:

• chr6-160753839-C-G
• rs11902
• NM_000301.5:c.*778C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• hypoplasminogenemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• angioedema, hereditary, 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000287558 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000301.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLG	NM_000301.5	MANE Select	c.*778C>G		3_prime_UTR	Exon 19 of 19	NP_000292.1	P00747

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLG	ENST00000308192.14	TSL:1 MANE Select	c.*778C>G		3_prime_UTR	Exon 19 of 19	ENSP00000308938.9	P00747
	PLG	ENST00000872435.1		c.*778C>G		3_prime_UTR	Exon 19 of 19	ENSP00000542494.1
	PLG	ENST00000418964.2	TSL:4	c.*778C>G		3_prime_UTR	Exon 19 of 19	ENSP00000389424.2	A6PVI2

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

African (AFR) AF: 0.454 AC: 18809 AN: 41454

American (AMR) AF: 0.655 AC: 10009 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1725 AN: 3470

East Asian (EAS) AF: 0.980 AC: 5080 AN: 5182

South Asian (SAS) AF: 0.680 AC: 3282 AN: 4824

European-Finnish (FIN) AF: 0.531 AC: 5607 AN: 10550

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35979 AN: 67972

Other (OTH) AF: 0.569 AC: 1201 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.38
PhyloP100		-0.38

Splicing

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

Other links and lift over

dbSNP: rs11902; hg19: chr6-161174871;