rs1545593

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005529.7(HSPG2):​c.64-10867A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,002 control chromosomes in the GnomAD database, including 16,514 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16514 hom., cov: 32)

Consequence

HSPG2
NM_005529.7 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114
Variant links:
Genes affected
HSPG2 (HGNC:5273): (heparan sulfate proteoglycan 2) This gene encodes the perlecan protein, which consists of a core protein to which three long chains of glycosaminoglycans (heparan sulfate or chondroitin sulfate) are attached. The perlecan protein is a large multidomain proteoglycan that binds to and cross-links many extracellular matrix components and cell-surface molecules. It has been shown that this protein interacts with laminin, prolargin, collagen type IV, FGFBP1, FBLN2, FGF7 and transthyretin, etc., and it plays essential roles in multiple biological activities. Perlecan is a key component of the vascular extracellular matrix, where it helps to maintain the endothelial barrier function. It is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain vascular homeostasis. It can also promote growth factor (e.g., FGF2) activity and thus stimulate endothelial growth and re-generation. It is a major component of basement membranes, where it is involved in the stabilization of other molecules as well as being involved with glomerular permeability to macromolecules and cell adhesion. Mutations in this gene cause Schwartz-Jampel syndrome type 1, Silverman-Handmaker type of dyssegmental dysplasia, and tardive dyskinesia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSPG2NM_005529.7 linkc.64-10867A>C intron_variant ENST00000374695.8 NP_005520.4 P98160

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HSPG2ENST00000374695.8 linkc.64-10867A>C intron_variant 1 NM_005529.7 ENSP00000363827.3 P98160

Frequencies

GnomAD3 genomes
AF:
0.449
AC:
68146
AN:
151884
Hom.:
16492
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.599
Gnomad AMI
AF:
0.486
Gnomad AMR
AF:
0.511
Gnomad ASJ
AF:
0.258
Gnomad EAS
AF:
0.700
Gnomad SAS
AF:
0.406
Gnomad FIN
AF:
0.363
Gnomad MID
AF:
0.297
Gnomad NFE
AF:
0.351
Gnomad OTH
AF:
0.421
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.449
AC:
68218
AN:
152002
Hom.:
16514
Cov.:
32
AF XY:
0.450
AC XY:
33478
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.599
Gnomad4 AMR
AF:
0.512
Gnomad4 ASJ
AF:
0.258
Gnomad4 EAS
AF:
0.700
Gnomad4 SAS
AF:
0.406
Gnomad4 FIN
AF:
0.363
Gnomad4 NFE
AF:
0.351
Gnomad4 OTH
AF:
0.419
Alfa
AF:
0.364
Hom.:
16770
Bravo
AF:
0.465
Asia WGS
AF:
0.521
AC:
1814
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.8
DANN
Benign
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1545593; hg19: chr1-22233670; API