dbSNP rs12501123: HPSE:c.374-32C>T (chr4-83319501-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.88

Publications

13 publications found

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 was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HPSE	NM_001098540.3 link	c.374-32C>T	intron_variant	Intron 2 of 11	ENST00000311412.10	NP_001092010.1	Q9Y251-1
HPSE	NM_006665.6 link	c.374-32C>T	intron_variant	Intron 3 of 12		NP_006656.2	Q9Y251-1
HPSE	NM_001199830.1 link	c.374-32C>T	intron_variant	Intron 2 of 10		NP_001186759.1	Q9Y251-2
HPSE	NM_001166498.3 link	c.374-32C>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.374-32C>T		intron_variant	Intron 2 of 11	1	NM_001098540.3	ENSP00000308107.5		Q9Y251-1

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120877

AN:

152042

Hom.:

48203

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.781

AC XY:

563263

AN XY:

721600

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

10136

20272

30409

40545

50681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20338

40676

61014

81352

101690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.795

AC:

120965

AN:

152160

Hom.:

48238

Cov.:

AF XY:

0.793

AC XY:

59014

AN XY:

74376

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1274

2548

3823

5097

6371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0010

(source)

DANN

Benign

0.40

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over