Variant chr4-83313106-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001098540.3(HPSE):c.673+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,576,334 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 31 hom. )

Consequence

HPSE
NM_001098540.3 splice_region, intron

Scores

Splicing: ADA: 0.00006639

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.447

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-83313106-G-T is Benign according to our data. Variant chr4-83313106-G-T is described in ClinVar as [Benign]. Clinvar id is 714087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HPSE	NM_001098540.3 linkuse as main transcript	c.673+8C>A	splice_region_variant, intron_variant	ENST00000311412.10
HPSE	NM_001166498.3 linkuse as main transcript	c.673+8C>A	splice_region_variant, intron_variant
HPSE	NM_001199830.1 linkuse as main transcript	c.500-2216C>A	intron_variant
HPSE	NM_006665.6 linkuse as main transcript	c.673+8C>A	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE	ENST00000311412.10 linkuse as main transcript	c.673+8C>A		splice_region_variant, intron_variant		1	NM_001098540.3	P1	Q9Y251-1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

539

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00590

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00133

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00518

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00315

AC:

779

AN:

247364

Hom.:

AF XY:

0.00295

AC XY:

395

AN XY:

133768

show subpopulations

Gnomad AFR exome

AF:

0.000991

Gnomad AMR exome

AF:

0.00366

Gnomad ASJ exome

AF:

0.00671

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.00467

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00489

AC:

6960

AN:

1424184

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

3359

AN XY:

710736

show subpopulations

Gnomad4 AFR exome

AF:

0.000707

Gnomad4 AMR exome

AF:

0.00392

Gnomad4 ASJ exome

AF:

0.00712

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00188

Gnomad4 NFE exome

AF:

0.00578

Gnomad4 OTH exome

AF:

0.00408

GnomAD4 genome

AF:

0.00354

AC:

539

AN:

152150

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

268

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00589

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00133

Gnomad4 NFE

AF:

0.00518

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00410

Hom.:

Bravo

AF:

0.00406

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.5

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000066

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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