chr4-83331997-C-T

Variant names:

• chr4-83331997-C-T
• rs4693612
• NM_001098540.3:c.227+2559G>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.227+2559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,200 control chromosomes in the GnomAD database, including 54,312 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 0.84 (54312 hom., cov: 32)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.227+2559G>A		intron_variant	Intron 1 of 11	ENST00000311412.10	NP_001092010.1
HPSE	NM_006665.6	c.227+2559G>A		intron_variant	Intron 2 of 12		NP_006656.2
HPSE	NM_001199830.1	c.227+2559G>A		intron_variant	Intron 1 of 10		NP_001186759.1
HPSE	NM_001166498.3	c.227+2559G>A		intron_variant	Intron 2 of 10		NP_001159970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.227+2559G>A		intron_variant	Intron 1 of 11	1	NM_001098540.3	ENSP00000308107.5

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127691 AN: 152082 Hom.: 54303 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.839 AC: 127730 AN: 152200 Hom.: 54312 Cov.: 32 AF XY: 0.839 AC XY: 62427 AN XY: 74418

African (AFR) AF: 0.686 AC: 28453 AN: 41474

American (AMR) AF: 0.887 AC: 13574 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3132 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5123 AN: 5190

South Asian (SAS) AF: 0.871 AC: 4203 AN: 4828

European-Finnish (FIN) AF: 0.869 AC: 9206 AN: 10598

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61140 AN: 68024

Other (OTH) AF: 0.866 AC: 1828 AN: 2112

Alfa AF: 0.882 Hom.: 110270

Bravo AF: 0.835

Asia WGS AF: 0.915 AC: 3182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.45
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4693612; hg19: chr4-84253150;