chr4-83315371-A-G

Variant names:

• chr4-83315371-A-G
• rs7691732
• NM_001098540.3:c.500-2084T>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.500-2084T>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 151,992 control chromosomes in the GnomAD database, including 48,425 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 (48425 hom., cov: 30)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• 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]

LOC105377313 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• 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.500-2084T>C		intron	N/A	NP_001092010.1
	HPSE	NM_006665.6		c.500-2084T>C		intron	N/A	NP_006656.2
	HPSE	NM_001199830.1		c.499+3973T>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.500-2084T>C		intron	N/A	ENSP00000308107.5
	HPSE	ENST00000405413.6	TSL:1	c.500-2084T>C		intron	N/A	ENSP00000384262.2
	HPSE	ENST00000513463.1	TSL:1	c.499+3973T>C		intron	N/A	ENSP00000421365.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121040 AN: 151874 Hom.: 48391 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.797 AC: 121127 AN: 151992 Hom.: 48425 Cov.: 30 AF XY: 0.795 AC XY: 59061 AN XY: 74276

African (AFR) AF: 0.855 AC: 35405 AN: 41420

American (AMR) AF: 0.742 AC: 11333 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2758 AN: 3464

East Asian (EAS) AF: 0.873 AC: 4517 AN: 5174

South Asian (SAS) AF: 0.809 AC: 3900 AN: 4820

European-Finnish (FIN) AF: 0.760 AC: 8010 AN: 10546

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

European-Non Finnish (NFE) AF: 0.776 AC: 52779 AN: 67994

Other (OTH) AF: 0.782 AC: 1647 AN: 2106

Alfa AF: 0.789 Hom.: 5885

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	-0.98
CADD	Benign	2.2
DANN	Benign	0.36
PhyloP100		-0.17
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: rs7691732; hg19: chr4-84236524;