dbSNP rs4693608: HPSE:c.374-735C>T (chr4-83320204-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001098540.3(HPSE):c.374-735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,676 control chromosomes in the GnomAD database, including 29,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.61 ( 29171 hom., cov: 31)

Consequence

HPSE
NM_001098540.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.107

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]

HPSE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 4-83320204-G-A is Benign according to our data. Variant chr4-83320204-G-A is described in ClinVar as [Benign]. Clinvar id is 1235597.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HPSE	NM_001098540.3 link	c.374-735C>T	intron_variant	Intron 2 of 11	ENST00000311412.10	NP_001092010.1	Q9Y251-1
HPSE	NM_006665.6 link	c.374-735C>T	intron_variant	Intron 3 of 12		NP_006656.2	Q9Y251-1
HPSE	NM_001199830.1 link	c.374-735C>T	intron_variant	Intron 2 of 10		NP_001186759.1	Q9Y251-2
HPSE	NM_001166498.3 link	c.374-735C>T	intron_variant	Intron 3 of 10		NP_001159970.1	Q9Y251-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10 link	c.374-735C>T		intron_variant	Intron 2 of 11	1	NM_001098540.3	ENSP00000308107.5		Q9Y251-1

Frequencies

GnomAD3 genomes

AF:

0.610

AC:

92513

AN:

151558

Hom.:

29128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.576

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

GnomAD4 genome

AF:

0.611

AC:

92609

AN:

151676

Hom.:

29171

Cov.:

AF XY:

0.611

AC XY:

45299

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.525

Gnomad4 EAS

AF:

0.794

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.529

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.580

Alfa

AF:

0.540

Hom.:

44124

Bravo

AF:

0.617

Asia WGS

AF:

0.736

AC:

2556

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29955035) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.3

DANN

Benign

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over