rs4693608

Positions:

• chr4-83320204-G-A
• chr4-83320204-G-C
• chr4-83320204-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.107

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE	NM_001098540.3	c.374-735C>T		intron_variant		ENST00000311412.10
HPSE	NM_001166498.3	c.374-735C>T		intron_variant
HPSE	NM_001199830.1	c.374-735C>T		intron_variant
HPSE	NM_006665.6	c.374-735C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE	ENST00000311412.10	c.374-735C>T		intron_variant		1	NM_001098540.3	P1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92513 AN: 151558 Hom.: 29128 Cov.: 31

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.: 31 AF XY: 0.611 AC XY: 45299 AN XY: 74100

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

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

Other links and lift over

dbSNP: rs4693608; hg19: chr4-84241357;