rs7691732

chr4-83315371-A-Gchr4-83315371-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE	NM_001098540.3	c.500-2084T>C		intron_variant		ENST00000311412.10
LOC105377313	XR_938944.2	n.27-1077A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE	ENST00000311412.10	c.500-2084T>C		intron_variant		1	NM_001098540.3	P1

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

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.782

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.2
Dann	Benign	0.36

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: rs7691732; hg19: chr4-84236524;