chr6-160706391-G-A

Position:

• chr6-160706391-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000301.5(PLG):​c.50-16G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,612,034 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (6 hom.)
• Consequence: PLG NM_000301.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-160706391-G-A is Benign according to our data. Variant chr6-160706391-G-A is described in ClinVar as [Benign]. Clinvar id is 1989227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLG	NM_000301.5	c.50-16G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000308192.14
PLG	NM_001168338.1	c.50-16G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLG	ENST00000308192.14	c.50-16G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000301.5	P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152112 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00215 AC: 541 AN: 251158 Hom.: 2 AF XY: 0.00212 AC XY: 288 AN XY: 135730

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00565

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0133

Gnomad NFE exome AF: 0.00128

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00144 AC: 2108 AN: 1459804 Hom.: 6 Cov.: 31 AF XY: 0.00145 AC XY: 1054 AN XY: 726288

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00555

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000743

Gnomad4 FIN exome AF: 0.0131

Gnomad4 NFE exome AF: 0.000985

Gnomad4 OTH exome AF: 0.00120

GnomAD4 genome AF: 0.00188 AC: 286 AN: 152230 Hom.: 2 Cov.: 32 AF XY: 0.00238 AC XY: 177 AN XY: 74412

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.0142

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00219 Hom.: 0

Bravo AF: 0.000729

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.012
DANN	Benign	0.23

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: rs139837651; hg19: chr6-161127423;