rs9991877

Positions:

• chr4-83295935-A-G

Variant summary

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

The NM_001098540.3(HPSE):​c.1473-432T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,098 control chromosomes in the GnomAD database, including 32,144 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 0.63 (32144 hom., cov: 32)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE	NM_001098540.3	c.1473-432T>C		intron_variant		ENST00000311412.10
HPSE	NM_001166498.3	c.1251-432T>C		intron_variant
HPSE	NM_001199830.1	c.1299-432T>C		intron_variant
HPSE	NM_006665.6	c.1473-432T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE	ENST00000311412.10	c.1473-432T>C		intron_variant		1	NM_001098540.3	P1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96474 AN: 151980 Hom.: 32138 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.635 AC: 96507 AN: 152098 Hom.: 32144 Cov.: 32 AF XY: 0.643 AC XY: 47827 AN XY: 74344

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.655

Alfa AF: 0.634 Hom.: 5221

Bravo AF: 0.613

Asia WGS AF: 0.779 AC: 2710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.86

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: rs9991877; hg19: chr4-84217088;