chr6-160706093-G-A

Variant names:

• chr6-160706093-G-A
• rs4252066
• ENST00000484367.5:n.706G>A

Variant summary

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

The ENST00000484367.5(PLG):​n.706G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 377,368 control chromosomes in the GnomAD database, including 10,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3911 hom., cov: 32)
  • Exomes 𝑓: 0.23 (6778 hom.)
• Consequence: PLG ENST00000484367.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600
• 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: 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=-0.94).
• BP6: Variant 6-160706093-G-A is Benign according to our data. Variant chr6-160706093-G-A is described in ClinVar as [Benign]. Clinvar id is 1247104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLG	NM_000301.5	c.50-314G>A		intron_variant	Intron 1 of 18	ENST00000308192.14	NP_000292.1
PLG	NM_001168338.1	c.50-314G>A		intron_variant	Intron 1 of 3		NP_001161810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14	c.50-314G>A		intron_variant	Intron 1 of 18	1	NM_000301.5	ENSP00000308938.9

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31756 AN: 151986 Hom.: 3916 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.225 AC: 50690 AN: 225264 Hom.: 6778 Cov.: 0 AF XY: 0.216 AC XY: 25792 AN XY: 119280

African (AFR) AF: 0.0994 AC: 709 AN: 7130

American (AMR) AF: 0.148 AC: 1346 AN: 9066

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 1681 AN: 6514

East Asian (EAS) AF: 0.000401 AC: 5 AN: 12460

South Asian (SAS) AF: 0.0980 AC: 3042 AN: 31046

European-Finnish (FIN) AF: 0.260 AC: 3496 AN: 13468

Middle Eastern (MID) AF: 0.245 AC: 216 AN: 882

European-Non Finnish (NFE) AF: 0.282 AC: 37219 AN: 132176

Other (OTH) AF: 0.238 AC: 2976 AN: 12522

GnomAD4 genome AF: 0.209 AC: 31750 AN: 152104 Hom.: 3911 Cov.: 32 AF XY: 0.204 AC XY: 15173 AN XY: 74334

African (AFR) AF: 0.102 AC: 4245 AN: 41510

American (AMR) AF: 0.195 AC: 2985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1001 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5184

South Asian (SAS) AF: 0.101 AC: 489 AN: 4822

European-Finnish (FIN) AF: 0.256 AC: 2700 AN: 10562

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.288 AC: 19579 AN: 67962

Other (OTH) AF: 0.224 AC: 472 AN: 2110

Alfa AF: 0.246 Hom.: 624

Bravo AF: 0.202

Asia WGS AF: 0.0460 AC: 165 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	-0.94
CADD	Benign	3.3
DANN	Benign	0.26
PhyloP100		-0.060
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: rs4252066; hg19: chr6-161127125;