rs783147

Variant names:

• chr6-160716958-G-A
• rs783147
• NM_000301.5:c.787+195G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-160716958-G-A
• chr6-160716958-G-C
• chr6-160716958-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000301.5(PLG):​c.787+195G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,088 control chromosomes in the GnomAD database, including 12,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (12742 hom., cov: 32)
• Consequence: PLG NM_000301.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.50
• Publications: 32 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: Orphanet, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• angioedema, hereditary, 4

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 6-160716958-G-A is Benign according to our data. Variant chr6-160716958-G-A is described in ClinVar as Benign. ClinVar VariationId is 1274066.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLG	NM_000301.5	c.787+195G>A		intron_variant	Intron 7 of 18	ENST00000308192.14	NP_000292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14	c.787+195G>A		intron_variant	Intron 7 of 18	1	NM_000301.5	ENSP00000308938.9
PLG	ENST00000418964.2	c.838+195G>A		intron_variant	Intron 7 of 18	4		ENSP00000389424.2
PLG	ENST00000297289.9	c.50-5450G>A		intron_variant	Intron 1 of 10	5		ENSP00000516619.1
PLG	ENST00000706906.1	n.787+195G>A		intron_variant	Intron 7 of 18			ENSP00000516618.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59776 AN: 151968 Hom.: 12746 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.393 AC: 59790 AN: 152088 Hom.: 12742 Cov.: 32 AF XY: 0.397 AC XY: 29528 AN XY: 74358

African (AFR) AF: 0.218 AC: 9031 AN: 41498

American (AMR) AF: 0.530 AC: 8100 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1535 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2733 AN: 5162

South Asian (SAS) AF: 0.402 AC: 1937 AN: 4816

European-Finnish (FIN) AF: 0.470 AC: 4965 AN: 10564

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30153 AN: 67974

Other (OTH) AF: 0.426 AC: 897 AN: 2108

Alfa AF: 0.435 Hom.: 66377

Bravo AF: 0.396

Asia WGS AF: 0.471 AC: 1640 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.027
DANN	Benign	0.32
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs783147; hg19: chr6-161137990;