rs4328905

Positions:

• chr4-83322396-A-G
• chr4-83322396-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098540.3(HPSE):​c.228-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,570,638 control chromosomes in the GnomAD database, including 20,075 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 0.18 (3151 hom., cov: 30)
  • Exomes 𝑓: 0.14 (16924 hom.)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

Genes affected

HPSE (HGNC:5164): (heparanase) Heparan sulfate proteoglycans are major components of the basement membrane and extracellular matrix. The protein encoded by this gene is an enzyme that cleaves heparan sulfate proteoglycans to permit cell movement through remodeling of the extracellular matrix. In addition, this cleavage can release bioactive molecules from the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

HPSE (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.228-32T>C		intron_variant		ENST00000311412.10	NP_001092010.1
HPSE	NM_006665.6	c.228-32T>C		intron_variant			NP_006656.2
HPSE	NM_001199830.1	c.228-32T>C		intron_variant			NP_001186759.1
HPSE	NM_001166498.3	c.228-32T>C		intron_variant			NP_001159970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.228-32T>C		intron_variant		1	NM_001098540.3	ENSP00000308107.5

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27755 AN: 151876 Hom.: 3146 Cov.: 30

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.0798

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.172

GnomAD3 exomes AF: 0.181 AC: 39142 AN: 215812 Hom.: 4467 AF XY: 0.178 AC XY: 20850 AN XY: 117010

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.422

Gnomad SAS exome AF: 0.262

Gnomad FIN exome AF: 0.0823

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.139 AC: 197861 AN: 1418644 Hom.: 16924 Cov.: 26 AF XY: 0.142 AC XY: 99707 AN XY: 704030

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.0798

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.183 AC: 27777 AN: 151994 Hom.: 3151 Cov.: 30 AF XY: 0.184 AC XY: 13698 AN XY: 74284

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.0798

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.174

Alfa AF: 0.132 Hom.: 1591

Bravo AF: 0.196

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4328905; hg19: chr4-84243549; COSMIC: COSV60986649;