rs4693611

chr4-83326567-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098540.3(HPSE):c.228-4203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,114 control chromosomes in the GnomAD database, including 3,974 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 0.20 (3974 hom., cov: 32)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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

Verdict is Benign. Variant got -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 = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE	NM_001098540.3	c.228-4203G>A		intron_variant		ENST00000311412.10
HPSE	NM_001166498.3	c.228-4203G>A		intron_variant
HPSE	NM_001199830.1	c.228-4203G>A		intron_variant
HPSE	NM_006665.6	c.228-4203G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE	ENST00000311412.10	c.228-4203G>A		intron_variant		1	NM_001098540.3	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30301 AN: 151996 Hom.: 3968 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.199 AC: 30328 AN: 152114 Hom.: 3974 Cov.: 32 AF XY: 0.200 AC XY: 14862 AN XY: 74374

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.0794

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.187

Alfa AF: 0.144 Hom.: 1140

Bravo AF: 0.215

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.9
Dann	Benign	0.96

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: rs4693611; hg19: chr4-84247720;