chr6-160731417-G-A

Position:

• chr6-160731417-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000301.5(PLG):​c.1438+185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,100 control chromosomes in the GnomAD database, including 33,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (33240 hom., cov: 32)
• Consequence: PLG NM_000301.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-160731417-G-A is Benign according to our data. Variant chr6-160731417-G-A is described in ClinVar as [Benign]. Clinvar id is 1281101.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
PLG	NM_000301.5	c.1438+185G>A		intron_variant		ENST00000308192.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLG	ENST00000308192.14	c.1438+185G>A		intron_variant		1	NM_000301.5	P1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98318 AN: 151982 Hom.: 33186 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.647 AC: 98433 AN: 152100 Hom.: 33240 Cov.: 32 AF XY: 0.651 AC XY: 48415 AN XY: 74336

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.656

Alfa AF: 0.561 Hom.: 33670

Bravo AF: 0.668

Asia WGS AF: 0.845 AC: 2936 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.88
CADD	Benign	0.63
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs783145; hg19: chr6-161152449;