4-83310951-T-C

Variant names:

• chr4-83310951-T-C
• rs6535455
• NM_001098540.3:c.674-61A>G

Variant summary

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

The NM_001098540.3(HPSE):​c.674-61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,324,120 control chromosomes in the GnomAD database, including 407,992 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 0.80 (48316 hom., cov: 33)
  • Exomes 𝑓: 0.78 (359676 hom.)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 13 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 = 0.851 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.674-61A>G		intron	N/A	NP_001092010.1	Q9Y251-1
	HPSE	NM_006665.6		c.674-61A>G		intron	N/A	NP_006656.2	Q9Y251-1
	HPSE	NM_001199830.1		c.500-61A>G		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.674-61A>G		intron	N/A	ENSP00000308107.5	Q9Y251-1
	HPSE	ENST00000405413.6	TSL:1	c.674-61A>G		intron	N/A	ENSP00000384262.2	Q9Y251-1
	HPSE	ENST00000513463.1	TSL:1	c.500-61A>G		intron	N/A	ENSP00000421365.1	Q9Y251-2

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121004 AN: 152082 Hom.: 48283 Cov.: 33

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.783 AC: 917656 AN: 1171920 Hom.: 359676 AF XY: 0.783 AC XY: 462859 AN XY: 590826

African (AFR) AF: 0.856 AC: 22661 AN: 26474

American (AMR) AF: 0.713 AC: 23946 AN: 33576

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 17371 AN: 21770

East Asian (EAS) AF: 0.846 AC: 32187 AN: 38058

South Asian (SAS) AF: 0.792 AC: 57550 AN: 72682

European-Finnish (FIN) AF: 0.765 AC: 38736 AN: 50622

Middle Eastern (MID) AF: 0.781 AC: 3900 AN: 4992

European-Non Finnish (NFE) AF: 0.780 AC: 681588 AN: 873430

Other (OTH) AF: 0.789 AC: 39717 AN: 50316

GnomAD4 genome AF: 0.796 AC: 121089 AN: 152200 Hom.: 48316 Cov.: 33 AF XY: 0.794 AC XY: 59062 AN XY: 74412

African (AFR) AF: 0.851 AC: 35360 AN: 41542

American (AMR) AF: 0.743 AC: 11352 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2758 AN: 3472

East Asian (EAS) AF: 0.872 AC: 4522 AN: 5186

South Asian (SAS) AF: 0.809 AC: 3902 AN: 4824

European-Finnish (FIN) AF: 0.760 AC: 8037 AN: 10570

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52724 AN: 68002

Other (OTH) AF: 0.784 AC: 1656 AN: 2112

Alfa AF: 0.785 Hom.: 5506

Bravo AF: 0.795

Asia WGS AF: 0.850 AC: 2954 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	0.90
DANN	Benign	0.77
PhyloP100		-2.3
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: rs6535455; hg19: chr4-84232104;