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GeneBe

rs11031

chr4-83301055-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001098540.3(HPSE):c.1377T>C(p.Asn459=) 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 (★).

Frequency

Genomes: 𝑓 0.073 ( 1380 hom., cov: 31)
Exomes 𝑓: 0.0078 ( 1175 hom. )

Consequence

HPSE
NM_001098540.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.668
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-83301055-A-G is Benign according to our data. Variant chr4-83301055-A-G is described in ClinVar as [Benign]. Clinvar id is 3037827.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.668 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
HPSENM_001098540.3 linkuse as main transcriptc.1377T>C p.Asn459= synonymous_variant 11/12 ENST00000311412.10
HPSENM_006665.6 linkuse as main transcriptc.1377T>C p.Asn459= synonymous_variant 12/13
HPSENM_001199830.1 linkuse as main transcriptc.1203T>C p.Asn401= synonymous_variant 10/11
HPSENM_001166498.3 linkuse as main transcriptc.1155T>C p.Asn385= synonymous_variant 10/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HPSEENST00000311412.10 linkuse as main transcriptc.1377T>C p.Asn459= synonymous_variant 11/121 NM_001098540.3 P1Q9Y251-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0727
AC:
11065
AN:
152108
Hom.:
1371
Cov.:
31
show subpopulations
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
GnomAD3 exomes
AF:
0.0193
AC:
4785
AN:
248048
Hom.:
563
AF XY:
0.0143
AC XY:
1915
AN XY:
134166
show subpopulations
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 SAS exome
AF:
0.000900
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
show subpopulations
Gnomad4 AFR exome
AF:
0.253
Gnomad4 AMR exome
AF:
0.0151
Gnomad4 ASJ exome
AF:
0.00288
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000865
Gnomad4 FIN exome
AF:
0.000431
Gnomad4 NFE exome
AF:
0.000808
Gnomad4 OTH exome
AF:
0.0187
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0729
AC:
11103
AN:
152224
Hom.:
1380
Cov.:
31
AF XY:
0.0711
AC XY:
5291
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.252
Gnomad4 AMR
AF:
0.0269
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.00147
Gnomad4 OTH
AF:
0.0516
Alfa
AF:
0.0346
Hom.:
354
Bravo
AF:
0.0836
Asia WGS
AF:
0.0160
AC:
59
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

HPSE-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 06, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
4.3
Dann
Benign
0.38

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11031; hg19: chr4-84222208; API