rs11031

Variant names:

• chr4-83301055-A-G
• rs11031
• NM_001098540.3:c.1377T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001098540.3(HPSE):​c.1377T>C​(p.Asn459Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,607,680 control chromosomes in the GnomAD database, including 2,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.073 (1380 hom., cov: 31)
  • Exomes 𝑓: 0.0078 (1175 hom.)
• Consequence: HPSE NM_001098540.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.668
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 4-83301055-A-G is Benign according to our data. Variant chr4-83301055-A-G is described in ClinVar as Benign. ClinVar VariationId is 3037827.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.668 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 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.1377T>C	p.Asn459Asn	synonymous	Exon 11 of 12	NP_001092010.1	Q9Y251-1
	HPSE	NM_006665.6		c.1377T>C	p.Asn459Asn	synonymous	Exon 12 of 13	NP_006656.2	Q9Y251-1
	HPSE	NM_001199830.1		c.1203T>C	p.Asn401Asn	synonymous	Exon 10 of 11	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.1377T>C	p.Asn459Asn	synonymous	Exon 11 of 12	ENSP00000308107.5	Q9Y251-1
	HPSE	ENST00000405413.6	TSL:1	c.1377T>C	p.Asn459Asn	synonymous	Exon 12 of 13	ENSP00000384262.2	Q9Y251-1
	HPSE	ENST00000513463.1	TSL:1	c.1203T>C	p.Asn401Asn	synonymous	Exon 10 of 11	ENSP00000421365.1	Q9Y251-2

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11065 AN: 152108 Hom.: 1371 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.0521

GnomAD2 exomes AF: 0.0193 AC: 4785 AN: 248048 AF XY: 0.0143

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.00289

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.00150

Gnomad OTH exome AF: 0.00849

GnomAD4 exome AF: 0.00777 AC: 11315 AN: 1455456 Hom.: 1175 Cov.: 28 AF XY: 0.00681 AC XY: 4930 AN XY: 724392

African (AFR) AF: 0.253 AC: 8312 AN: 32870

American (AMR) AF: 0.0151 AC: 665 AN: 44166

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 75 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.000865 AC: 74 AN: 85578

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53386

Middle Eastern (MID) AF: 0.0254 AC: 146 AN: 5744

European-Non Finnish (NFE) AF: 0.000808 AC: 895 AN: 1108006

Other (OTH) AF: 0.0187 AC: 1125 AN: 60168

GnomAD4 genome AF: 0.0729 AC: 11103 AN: 152224 Hom.: 1380 Cov.: 31 AF XY: 0.0711 AC XY: 5291 AN XY: 74440

African (AFR) AF: 0.252 AC: 10441 AN: 41478

American (AMR) AF: 0.0269 AC: 411 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00147 AC: 100 AN: 68024

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0354 Hom.: 455

Bravo AF: 0.0836

Asia WGS AF: 0.0160 AC: 59 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HPSE-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.3
DANN	Benign	0.38
PhyloP100		-0.67
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: rs11031; hg19: chr4-84222208;