4-83302560-C-T

Variant names:

• chr4-83302560-C-T
• rs4364254
• NM_001098540.3:c.1207-292G>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.1207-292G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,044 control chromosomes in the GnomAD database, including 31,331 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 0.63 (31331 hom., cov: 32)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 37 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 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.1207-292G>A		intron	N/A	NP_001092010.1	Q9Y251-1
	HPSE	NM_006665.6		c.1207-292G>A		intron	N/A	NP_006656.2	Q9Y251-1
	HPSE	NM_001199830.1		c.1033-292G>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.1207-292G>A		intron	N/A	ENSP00000308107.5	Q9Y251-1
	HPSE	ENST00000405413.6	TSL:1	c.1207-292G>A		intron	N/A	ENSP00000384262.2	Q9Y251-1
	HPSE	ENST00000513463.1	TSL:1	c.1033-292G>A		intron	N/A	ENSP00000421365.1	Q9Y251-2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96424 AN: 151926 Hom.: 31327 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.634 AC: 96444 AN: 152044 Hom.: 31331 Cov.: 32 AF XY: 0.634 AC XY: 47070 AN XY: 74298

African (AFR) AF: 0.487 AC: 20182 AN: 41452

American (AMR) AF: 0.666 AC: 10171 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2414 AN: 3470

East Asian (EAS) AF: 0.741 AC: 3836 AN: 5178

South Asian (SAS) AF: 0.682 AC: 3288 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6878 AN: 10566

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47759 AN: 67968

Other (OTH) AF: 0.630 AC: 1330 AN: 2110

Alfa AF: 0.642 Hom.: 29861

Bravo AF: 0.624

Asia WGS AF: 0.715 AC: 2484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.47
PhyloP100		-0.095
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4364254;

hg19: chr4-84223713;