NM_001098540.3:c.374-735C>T

Variant names:

• chr4-83320204-G-A
• rs4693608
• NM_001098540.3:c.374-735C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	NM_001098540.3	MANE Select	c.374-735C>T		intron	N/A	NP_001092010.1	Q9Y251-1
	HPSE	NM_006665.6		c.374-735C>T		intron	N/A	NP_006656.2	Q9Y251-1
	HPSE	NM_001199830.1		c.374-735C>T		intron	N/A	NP_001186759.1	Q9Y251-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	ENST00000311412.10	TSL:1 MANE Select	c.374-735C>T		intron	N/A	ENSP00000308107.5	Q9Y251-1
	HPSE	ENST00000405413.6	TSL:1	c.374-735C>T		intron	N/A	ENSP00000384262.2	Q9Y251-1
	HPSE	ENST00000513463.1	TSL:1	c.374-735C>T		intron	N/A	ENSP00000421365.1	Q9Y251-2

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

African (AFR) AF: 0.759 AC: 31349 AN: 41296

American (AMR) AF: 0.583 AC: 8884 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1819 AN: 3468

East Asian (EAS) AF: 0.794 AC: 4089 AN: 5152

South Asian (SAS) AF: 0.642 AC: 3094 AN: 4818

European-Finnish (FIN) AF: 0.529 AC: 5560 AN: 10502

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36127 AN: 67884

Other (OTH) AF: 0.580 AC: 1221 AN: 2106

Alfa AF: 0.554 Hom.: 104503

Bravo AF: 0.617

Asia WGS AF: 0.736 AC: 2556 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.58
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4693608; hg19: chr4-84241357;