4-83318929-C-T

Variant names:

• chr4-83318929-C-T
• rs4568236
• NM_001098540.3:c.499+415G>A

Variant summary

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

The NM_001098540.3(HPSE):​c.499+415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 151,958 control chromosomes in the GnomAD database, including 48,219 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 (48219 hom., cov: 29)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098540.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	NM_001098540.3	MANE Select	c.499+415G>A		intron	N/A	NP_001092010.1
	HPSE	NM_006665.6		c.499+415G>A		intron	N/A	NP_006656.2
	HPSE	NM_001199830.1		c.499+415G>A		intron	N/A	NP_001186759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	ENST00000311412.10	TSL:1 MANE Select	c.499+415G>A		intron	N/A	ENSP00000308107.5
	HPSE	ENST00000405413.6	TSL:1	c.499+415G>A		intron	N/A	ENSP00000384262.2
	HPSE	ENST00000513463.1	TSL:1	c.499+415G>A		intron	N/A	ENSP00000421365.1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120788 AN: 151840 Hom.: 48184 Cov.: 29

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.795 AC: 120876 AN: 151958 Hom.: 48219 Cov.: 29 AF XY: 0.794 AC XY: 58943 AN XY: 74254

African (AFR) AF: 0.849 AC: 35175 AN: 41426

American (AMR) AF: 0.742 AC: 11322 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2762 AN: 3472

East Asian (EAS) AF: 0.873 AC: 4510 AN: 5168

South Asian (SAS) AF: 0.809 AC: 3895 AN: 4814

European-Finnish (FIN) AF: 0.759 AC: 8001 AN: 10536

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52784 AN: 67964

Other (OTH) AF: 0.780 AC: 1648 AN: 2112

Alfa AF: 0.788 Hom.: 5865

Bravo AF: 0.795

Asia WGS AF: 0.850 AC: 2954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.9
DANN	Benign	0.53
PhyloP100		0.47
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: rs4568236; hg19: chr4-84240082;