rs12501123

Positions:

• chr4-83319501-G-A
• chr4-83319501-G-C

Variant summary

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

The NM_001098540.3(HPSE):​c.374-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,601,002 control chromosomes in the GnomAD database, including 490,395 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 0.79 (48238 hom., cov: 31)
  • Exomes 𝑓: 0.78 (442157 hom.)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88

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=-0.99).
• 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.374-32C>T		intron_variant		ENST00000311412.10
HPSE	NM_001166498.3	c.374-32C>T		intron_variant
HPSE	NM_001199830.1	c.374-32C>T		intron_variant
HPSE	NM_006665.6	c.374-32C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE	ENST00000311412.10	c.374-32C>T		intron_variant		1	NM_001098540.3	P1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120877 AN: 152042 Hom.: 48203 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.780

GnomAD3 exomes AF: 0.781 AC: 194966 AN: 249636 Hom.: 76386 AF XY: 0.783 AC XY: 105715 AN XY: 135036

Gnomad AFR exome AF: 0.854

Gnomad AMR exome AF: 0.702

Gnomad ASJ exome AF: 0.799

Gnomad EAS exome AF: 0.871

Gnomad SAS exome AF: 0.796

Gnomad FIN exome AF: 0.763

Gnomad NFE exome AF: 0.778

Gnomad OTH exome AF: 0.770

GnomAD4 exome AF: 0.780 AC: 1130556 AN: 1448842 Hom.: 442157 Cov.: 27 AF XY: 0.781 AC XY: 563263 AN XY: 721600

Gnomad4 AFR exome AF: 0.852

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.799

Gnomad4 EAS exome AF: 0.847

Gnomad4 SAS exome AF: 0.788

Gnomad4 FIN exome AF: 0.764

Gnomad4 NFE exome AF: 0.778

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.795 AC: 120965 AN: 152160 Hom.: 48238 Cov.: 31 AF XY: 0.793 AC XY: 59014 AN XY: 74376

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.781

Alfa AF: 0.785 Hom.: 11163

Bravo AF: 0.794

Asia WGS AF: 0.849 AC: 2952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0010
DANN	Benign	0.40

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: rs12501123; hg19: chr4-84240654;