rs4693611

Variant names:

• chr4-83326567-C-T
• rs4693611
• NM_001098540.3:c.228-4203G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098540.3(HPSE):​c.228-4203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,114 control chromosomes in the GnomAD database, including 3,974 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 0.20 (3974 hom., cov: 32)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 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.228-4203G>A		intron	N/A	NP_001092010.1	Q9Y251-1
	HPSE	NM_006665.6		c.228-4203G>A		intron	N/A	NP_006656.2	Q9Y251-1
	HPSE	NM_001199830.1		c.228-4203G>A		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.228-4203G>A		intron	N/A	ENSP00000308107.5	Q9Y251-1
	HPSE	ENST00000405413.6	TSL:1	c.228-4203G>A		intron	N/A	ENSP00000384262.2	Q9Y251-1
	HPSE	ENST00000513463.1	TSL:1	c.228-4203G>A		intron	N/A	ENSP00000421365.1	Q9Y251-2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30301 AN: 151996 Hom.: 3968 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30328 AN: 152114 Hom.: 3974 Cov.: 32 AF XY: 0.200 AC XY: 14862 AN XY: 74374

African (AFR) AF: 0.341 AC: 14134 AN: 41450

American (AMR) AF: 0.197 AC: 3016 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2120 AN: 5168

South Asian (SAS) AF: 0.258 AC: 1240 AN: 4814

European-Finnish (FIN) AF: 0.0794 AC: 842 AN: 10608

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7943 AN: 67992

Other (OTH) AF: 0.187 AC: 394 AN: 2110

Alfa AF: 0.151 Hom.: 1763

Bravo AF: 0.215

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.9
DANN	Benign	0.96
PhyloP100		0.092
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: rs4693611; hg19: chr4-84247720;