dbSNP rs6856901: HPSE:c.*129G>C (chr4-83295215-C-G) – 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.*129G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 644,462 control chromosomes in the GnomAD database, including 21,954 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 0.27 ( 5837 hom., cov: 32)

Exomes 𝑓: 0.25 ( 16117 hom. )

Consequence

HPSE
NM_001098540.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

7 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:

Genome browser will be placed here

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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HPSE	NM_001098540.3	MANE Select	c.*129G>C	3_prime_UTR	Exon 12 of 12	NP_001092010.1	Q9Y251-1
HPSE	NM_006665.6		c.*129G>C	3_prime_UTR	Exon 13 of 13	NP_006656.2	Q9Y251-1
HPSE	NM_001199830.1		c.*129G>C	3_prime_UTR	Exon 11 of 11	NP_001186759.1	Q9Y251-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HPSE	ENST00000311412.10	TSL:1 MANE Select	c.*129G>C	3_prime_UTR	Exon 12 of 12	ENSP00000308107.5	Q9Y251-1
HPSE	ENST00000405413.6	TSL:1	c.*129G>C	3_prime_UTR	Exon 13 of 13	ENSP00000384262.2	Q9Y251-1
HPSE	ENST00000681769.1		c.1473-1620G>C	intron	N/A	ENSP00000506434.1	A0A7P0TBD9

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41211

AN:

151810

Hom.:

5822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.266

GnomAD4 exome

AF:

0.248

AC:

122110

AN:

492534

Hom.:

16117

Cov.:

AF XY:

0.246

AC XY:

63763

AN XY:

258804

show subpopulations

African (AFR)

AF:

0.338

AC:

4646

AN:

13760

American (AMR)

AF:

0.297

AC:

6472

AN:

21808

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

3810

AN:

13298

East Asian (EAS)

AF:

0.112

AC:

3695

AN:

32916

South Asian (SAS)

AF:

0.223

AC:

8562

AN:

38472

European-Finnish (FIN)

AF:

0.192

AC:

6663

AN:

34772

Middle Eastern (MID)

AF:

0.319

AC:

623

AN:

1952

European-Non Finnish (NFE)

AF:

0.261

AC:

80671

AN:

308738

Other (OTH)

AF:

0.260

AC:

6968

AN:

26818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4282

8565

12847

17130

21412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1118

2236

3354

4472

5590

<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:

0.272

AC:

41265

AN:

151928

Hom.:

5837

Cov.:

AF XY:

0.267

AC XY:

19842

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.336

AC:

13929

AN:

41394

American (AMR)

AF:

0.279

AC:

4267

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

982

AN:

3466

East Asian (EAS)

AF:

0.125

AC:

649

AN:

5184

South Asian (SAS)

AF:

0.225

AC:

1087

AN:

4826

European-Finnish (FIN)

AF:

0.179

AC:

1889

AN:

10548

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17550

AN:

67920

Other (OTH)

AF:

0.265

AC:

558

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1508

3015

4523

6030

7538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.123

Hom.:

208

Bravo

AF:

0.286

Asia WGS

AF:

0.180

AC:

624

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.25

(source)

DANN

Benign

0.70

PhyloP100

-1.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over