6-160722344-A-G

Position:

• chr6-160722344-A-G

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.1097-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,210,450 control chromosomes in the GnomAD database, including 41,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (4001 hom., cov: 32)
  • Exomes 𝑓: 0.25 (37225 hom.)
• Consequence: PLG NM_000301.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0120

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 6-160722344-A-G is Benign according to our data. Variant chr6-160722344-A-G is described in ClinVar as [Benign]. Clinvar id is 1258345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLG	NM_000301.5	c.1097-64A>G		intron_variant		ENST00000308192.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLG	ENST00000308192.14	c.1097-64A>G		intron_variant		1	NM_000301.5	P1
PLG	ENST00000297289.9	c.50-64A>G		intron_variant		5
PLG	ENST00000418964.2	c.1148-64A>G		intron_variant		4
PLG	ENST00000706906.1	c.1097-64A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32094 AN: 151968 Hom.: 4005 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.251 AC: 265523 AN: 1058364 Hom.: 37225 AF XY: 0.248 AC XY: 135280 AN XY: 545312

Gnomad4 AFR exome AF: 0.0974

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.000529

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.211 AC: 32085 AN: 152086 Hom.: 4001 Cov.: 32 AF XY: 0.207 AC XY: 15372 AN XY: 74334

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.225

Alfa AF: 0.274 Hom.: 6178

Bravo AF: 0.204

Asia WGS AF: 0.0460 AC: 162 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.56

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: rs4252117; hg19: chr6-161143376;