rs6535458

Variant names:

• chr4-83312296-T-C
• rs6535458
• NM_001098540.3:c.673+818A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-83312296-T-C
• chr4-83312296-T-G

Variant summary

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

The NM_001098540.3(HPSE):​c.673+818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,164 control chromosomes in the GnomAD database, including 48,462 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 0.80 (48462 hom., cov: 33)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 10 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.673+818A>G		intron_variant	Intron 4 of 11	ENST00000311412.10	NP_001092010.1
HPSE	NM_006665.6	c.673+818A>G		intron_variant	Intron 5 of 12		NP_006656.2
HPSE	NM_001199830.1	c.500-1406A>G		intron_variant	Intron 3 of 10		NP_001186759.1
HPSE	NM_001166498.3	c.673+818A>G		intron_variant	Intron 5 of 10		NP_001159970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.673+818A>G		intron_variant	Intron 4 of 11	1	NM_001098540.3	ENSP00000308107.5

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121166 AN: 152046 Hom.: 48427 Cov.: 33

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.797 AC: 121256 AN: 152164 Hom.: 48462 Cov.: 33 AF XY: 0.795 AC XY: 59131 AN XY: 74370

African (AFR) AF: 0.855 AC: 35515 AN: 41522

American (AMR) AF: 0.743 AC: 11358 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2757 AN: 3470

East Asian (EAS) AF: 0.873 AC: 4517 AN: 5176

South Asian (SAS) AF: 0.810 AC: 3904 AN: 4818

European-Finnish (FIN) AF: 0.759 AC: 8030 AN: 10578

Middle Eastern (MID) AF: 0.755 AC: 219 AN: 290

European-Non Finnish (NFE) AF: 0.776 AC: 52739 AN: 68004

Other (OTH) AF: 0.785 AC: 1659 AN: 2114

Alfa AF: 0.782 Hom.: 194742

Bravo AF: 0.796

Asia WGS AF: 0.850 AC: 2957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		0.38
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

Other links and lift over

dbSNP: rs6535458; hg19: chr4-84233449;