rs12501123

Variant names:

• chr4-83319501-G-A
• rs12501123
• NM_001098540.3:c.374-32C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098540.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	NM_001098540.3	MANE Select	c.374-32C>T		intron	N/A	NP_001092010.1	Q9Y251-1
	HPSE	NM_006665.6		c.374-32C>T		intron	N/A	NP_006656.2	Q9Y251-1
	HPSE	NM_001199830.1		c.374-32C>T		intron	N/A	NP_001186759.1	Q9Y251-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	ENST00000311412.10	TSL:1 MANE Select	c.374-32C>T		intron	N/A	ENSP00000308107.5	Q9Y251-1
	HPSE	ENST00000405413.6	TSL:1	c.374-32C>T		intron	N/A	ENSP00000384262.2	Q9Y251-1
	HPSE	ENST00000513463.1	TSL:1	c.374-32C>T		intron	N/A	ENSP00000421365.1	Q9Y251-2

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

GnomAD2 exomes AF: 0.781 AC: 194966 AN: 249636 AF XY: 0.783

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 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

African (AFR) AF: 0.852 AC: 28273 AN: 33180

American (AMR) AF: 0.705 AC: 31226 AN: 44294

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 20769 AN: 25994

East Asian (EAS) AF: 0.847 AC: 33531 AN: 39586

South Asian (SAS) AF: 0.788 AC: 67746 AN: 85920

European-Finnish (FIN) AF: 0.764 AC: 40592 AN: 53148

Middle Eastern (MID) AF: 0.786 AC: 4496 AN: 5722

European-Non Finnish (NFE) AF: 0.778 AC: 856676 AN: 1101090

Other (OTH) AF: 0.789 AC: 47247 AN: 59908

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

African (AFR) AF: 0.849 AC: 35233 AN: 41514

American (AMR) AF: 0.742 AC: 11334 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2759 AN: 3468

East Asian (EAS) AF: 0.873 AC: 4530 AN: 5188

South Asian (SAS) AF: 0.809 AC: 3900 AN: 4820

European-Finnish (FIN) AF: 0.759 AC: 8031 AN: 10578

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52750 AN: 67996

Other (OTH) AF: 0.781 AC: 1649 AN: 2112

Alfa AF: 0.787 Hom.: 19249

Bravo AF: 0.794

Asia WGS AF: 0.849 AC: 2952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0010
DANN	Benign	0.40
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12501123; hg19: chr4-84240654;