rs4434244

chr4-83305540-T-G

Variant summary

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

The NM_001098540.3(HPSE):c.1206+663A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,058 control chromosomes in the GnomAD database, including 37,251 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 0.69 (37251 hom., cov: 32)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE	NM_001098540.3	c.1206+663A>C		intron_variant		ENST00000311412.10
HPSE	NM_001166498.3	c.985-3272A>C		intron_variant
HPSE	NM_001199830.1	c.1032+663A>C		intron_variant
HPSE	NM_006665.6	c.1206+663A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE	ENST00000311412.10	c.1206+663A>C		intron_variant		1	NM_001098540.3	P1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105490 AN: 151940 Hom.: 37235 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.694 AC: 105552 AN: 152058 Hom.: 37251 Cov.: 32 AF XY: 0.699 AC XY: 51989 AN XY: 74334

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.716

Alfa AF: 0.715 Hom.: 9915

Bravo AF: 0.681

Asia WGS AF: 0.812 AC: 2821 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.12
Dann	Benign	0.45

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: rs4434244; hg19: chr4-84226693;