rs12507864

Positions:

• chr4-83333341-T-C

Variant summary

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

The ENST00000311412.10(HPSE):​c.227+1215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,156 control chromosomes in the GnomAD database, including 1,791 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 0.13 (1791 hom., cov: 32)
• Consequence: HPSE ENST00000311412.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.227+1215A>G		intron_variant		ENST00000311412.10	NP_001092010.1
HPSE	NM_001166498.3	c.227+1215A>G		intron_variant			NP_001159970.1
HPSE	NM_001199830.1	c.227+1215A>G		intron_variant			NP_001186759.1
HPSE	NM_006665.6	c.227+1215A>G		intron_variant			NP_006656.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.227+1215A>G		intron_variant		1	NM_001098540.3	ENSP00000308107	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20184 AN: 152038 Hom.: 1784 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0857

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.133 AC: 20216 AN: 152156 Hom.: 1791 Cov.: 32 AF XY: 0.132 AC XY: 9803 AN XY: 74408

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0857

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0960

Gnomad4 NFE AF: 0.0851

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0963 Hom.: 1072

Bravo AF: 0.138

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12507864; hg19: chr4-84254494;