rs11810496

Variant names:

• chr1-21897609-A-G
• rs11810496
• NM_005529.7:c.64-1299T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-21897609-A-G
• chr1-21897609-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005529.7(HSPG2):​c.64-1299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,120 control chromosomes in the GnomAD database, including 5,249 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 0.24 (5249 hom., cov: 32)
• Consequence: HSPG2 NM_005529.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 8 publications found

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]

HSPG2 Gene-Disease associations (from GenCC):

• Schwartz-Jampel syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Silverman-Handmaker type dyssegmental dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• Schwartz-Jampel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005529.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPG2	NM_005529.7	MANE Select	c.64-1299T>C		intron	N/A	NP_005520.4
	HSPG2	NM_001291860.2		c.64-1299T>C		intron	N/A	NP_001278789.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPG2	ENST00000374695.8	TSL:1 MANE Select	c.64-1299T>C		intron	N/A	ENSP00000363827.3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36305 AN: 152002 Hom.: 5246 Cov.: 32

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36304 AN: 152120 Hom.: 5249 Cov.: 32 AF XY: 0.243 AC XY: 18064 AN XY: 74350

African (AFR) AF: 0.0836 AC: 3471 AN: 41540

American (AMR) AF: 0.357 AC: 5460 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2019 AN: 5160

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4816

European-Finnish (FIN) AF: 0.301 AC: 3182 AN: 10560

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19139 AN: 67986

Other (OTH) AF: 0.236 AC: 498 AN: 2106

Alfa AF: 0.269 Hom.: 25028

Bravo AF: 0.235

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.86
DANN	Benign	0.67
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11810496; hg19: chr1-22224102;