rs4252117

Variant names:

• chr6-160722344-A-G
• rs4252117
• NM_000301.5:c.1097-64A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-160722344-A-G
• chr6-160722344-A-C
• chr6-160722344-A-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.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
• Publications: 14 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: ClinGen, Orphanet, 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=-0.88).
• BP6: Variant 6-160722344-A-G is Benign according to our data. Variant chr6-160722344-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000301.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLG	NM_000301.5	MANE Select	c.1097-64A>G		intron	N/A	NP_000292.1	P00747

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLG	ENST00000308192.14	TSL:1 MANE Select	c.1097-64A>G		intron	N/A	ENSP00000308938.9	P00747
	PLG	ENST00000872438.1		c.1097-64A>G		intron	N/A	ENSP00000542497.1
	PLG	ENST00000872435.1		c.1097-64A>G		intron	N/A	ENSP00000542494.1

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

African (AFR) AF: 0.0974 AC: 2505 AN: 25728

American (AMR) AF: 0.128 AC: 5590 AN: 43828

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 6878 AN: 23658

East Asian (EAS) AF: 0.000529 AC: 20 AN: 37794

South Asian (SAS) AF: 0.107 AC: 8355 AN: 78152

European-Finnish (FIN) AF: 0.262 AC: 13837 AN: 52820

Middle Eastern (MID) AF: 0.255 AC: 1268 AN: 4964

European-Non Finnish (NFE) AF: 0.290 AC: 215760 AN: 744402

Other (OTH) AF: 0.241 AC: 11310 AN: 47018

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

African (AFR) AF: 0.103 AC: 4253 AN: 41480

American (AMR) AF: 0.196 AC: 2996 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1059 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.103 AC: 495 AN: 4818

European-Finnish (FIN) AF: 0.262 AC: 2769 AN: 10574

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19760 AN: 67962

Other (OTH) AF: 0.225 AC: 476 AN: 2114

Alfa AF: 0.260 Hom.: 8314

Bravo AF: 0.204

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.012
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4252117;

hg19: chr6-161143376;