4-83317359-A-G

Variant names:

• chr4-83317359-A-G
• rs6535462
• NM_001098540.3:c.499+1985T>C

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+1985T>C 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 152,180 control chromosomes in the GnomAD database, including 48,506 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 (48506 hom., cov: 33)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	NM_001098540.3	MANE Select	c.499+1985T>C		intron	N/A	NP_001092010.1
	HPSE	NM_006665.6		c.499+1985T>C		intron	N/A	NP_006656.2
	HPSE	NM_001199830.1		c.499+1985T>C		intron	N/A	NP_001186759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	ENST00000311412.10	TSL:1 MANE Select	c.499+1985T>C		intron	N/A	ENSP00000308107.5
	HPSE	ENST00000405413.6	TSL:1	c.499+1985T>C		intron	N/A	ENSP00000384262.2
	HPSE	ENST00000513463.1	TSL:1	c.499+1985T>C		intron	N/A	ENSP00000421365.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121209 AN: 152062 Hom.: 48472 Cov.: 33

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.611

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: 0.774

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.797 AC: 121296 AN: 152180 Hom.: 48506 Cov.: 33 AF XY: 0.795 AC XY: 59161 AN XY: 74394

African (AFR) AF: 0.854 AC: 35483 AN: 41526

American (AMR) AF: 0.743 AC: 11354 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2761 AN: 3468

East Asian (EAS) AF: 0.873 AC: 4521 AN: 5178

South Asian (SAS) AF: 0.810 AC: 3899 AN: 4816

European-Finnish (FIN) AF: 0.759 AC: 8033 AN: 10582

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.777 AC: 52814 AN: 68008

Other (OTH) AF: 0.783 AC: 1653 AN: 2110

Alfa AF: 0.778 Hom.: 7769

Bravo AF: 0.796

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	-0.94
CADD	Benign	0.86
DANN	Benign	0.47
PhyloP100		-0.94
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: rs6535462; hg19: chr4-84238512;