6-160733923-C-T

Variant names:

• chr6-160733923-C-T
• rs1317026
• NM_000301.5:c.1588-72C>T

Variant summary

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

The ENST00000308192.14(PLG):​c.1588-72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 769,686 control chromosomes in the GnomAD database, including 4,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (2920 hom., cov: 30)
  • Exomes 𝑓: 0.041 (1849 hom.)
• Consequence: PLG ENST00000308192.14 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.04
• Publications: 5 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=-0.97).
• BP6: Variant 6-160733923-C-T is Benign according to our data. Variant chr6-160733923-C-T is described in ClinVar as Benign. ClinVar VariationId is 1265723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000308192.14. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLG	NM_000301.5	MANE Select	c.1588-72C>T		intron	N/A	NP_000292.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLG	ENST00000308192.14	TSL:1 MANE Select	c.1588-72C>T		intron	N/A	ENSP00000308938.9
	PLG	ENST00000418964.2	TSL:4	c.1639-72C>T		intron	N/A	ENSP00000389424.2
	PLG	ENST00000297289.9	TSL:5	c.541-72C>T		intron	N/A	ENSP00000516619.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18890 AN: 150818 Hom.: 2913 Cov.: 30

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0814

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.0414 AC: 25625 AN: 618762 Hom.: 1849 AF XY: 0.0400 AC XY: 13494 AN XY: 337180

African (AFR) AF: 0.373 AC: 6376 AN: 17076

American (AMR) AF: 0.0450 AC: 1885 AN: 41930

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 1650 AN: 19422

East Asian (EAS) AF: 0.000264 AC: 9 AN: 34090

South Asian (SAS) AF: 0.0445 AC: 3099 AN: 69632

European-Finnish (FIN) AF: 0.0160 AC: 807 AN: 50322

Middle Eastern (MID) AF: 0.173 AC: 682 AN: 3952

European-Non Finnish (NFE) AF: 0.0257 AC: 9023 AN: 350960

Other (OTH) AF: 0.0667 AC: 2094 AN: 31378

GnomAD4 genome AF: 0.125 AC: 18933 AN: 150924 Hom.: 2920 Cov.: 30 AF XY: 0.122 AC XY: 8963 AN XY: 73664

African (AFR) AF: 0.368 AC: 15031 AN: 40882

American (AMR) AF: 0.0684 AC: 1040 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.0814 AC: 281 AN: 3452

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5156

South Asian (SAS) AF: 0.0467 AC: 224 AN: 4792

European-Finnish (FIN) AF: 0.0191 AC: 198 AN: 10360

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1825 AN: 67788

Other (OTH) AF: 0.117 AC: 246 AN: 2094

Alfa AF: 0.0511 Hom.: 1159

Bravo AF: 0.140

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.68
PhyloP100		-2.0
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: rs1317026; hg19: chr6-161154955;