6-160733923-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000301.5(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
NM_000301.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.04

Publications

5 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLGNM_000301.5 linkc.1588-72C>T intron_variant Intron 12 of 18 ENST00000308192.14 NP_000292.1 P00747

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLGENST00000308192.14 linkc.1588-72C>T intron_variant Intron 12 of 18 1 NM_000301.5 ENSP00000308938.9 P00747

Frequencies

GnomAD3 genomes
AF:
0.125
AC:
18890
AN:
150818
Hom.:
2913
Cov.:
30
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.520
Heterozygous variant carriers
0
1197
2393
3590
4786
5983
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
178
356
534
712
890
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.125
AC:
18933
AN:
150924
Hom.:
2920
Cov.:
30
AF XY:
0.122
AC XY:
8963
AN XY:
73664
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.512
Heterozygous variant carriers
0
621
1242
1864
2485
3106
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
172
344
516
688
860
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0511
Hom.:
1159
Bravo
AF:
0.140
Asia WGS
AF:
0.0450
AC:
157
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jun 20, 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
-0.97
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

Publications

Other links and lift over

dbSNP: rs1317026; hg19: chr6-161154955; API