4-83292466-A-G

Variant names:

• chr4-83292466-A-G
• rs4693602
• NM_001098540.3:c.*2878T>C

Variant summary

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

The NM_001098540.3(HPSE):​c.*2878T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,178 control chromosomes in the GnomAD database, including 38,752 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 0.71 (38752 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: HPSE NM_001098540.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.*2878T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000311412.10	NP_001092010.1
HPSE	NM_006665.6	c.*2878T>C		3_prime_UTR_variant	Exon 13 of 13		NP_006656.2
HPSE	NM_001199830.1	c.*2878T>C		3_prime_UTR_variant	Exon 11 of 11		NP_001186759.1
HPSE	NM_001166498.3	c.*2878T>C		3_prime_UTR_variant	Exon 11 of 11		NP_001159970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.*2878T>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_001098540.3	ENSP00000308107.5
HPSE	ENST00000405413.6	c.*2878T>C		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000384262.2
HPSE	ENST00000681769.1	c.*1105T>C		downstream_gene_variant				ENSP00000506434.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108289 AN: 152060 Hom.: 38731 Cov.: 33

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.706

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.712 AC: 108364 AN: 152178 Hom.: 38752 Cov.: 33 AF XY: 0.719 AC XY: 53473 AN XY: 74406

African (AFR) AF: 0.693 AC: 28746 AN: 41496

American (AMR) AF: 0.705 AC: 10791 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2320 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4503 AN: 5190

South Asian (SAS) AF: 0.727 AC: 3501 AN: 4818

European-Finnish (FIN) AF: 0.805 AC: 8527 AN: 10588

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47674 AN: 67998

Other (OTH) AF: 0.707 AC: 1493 AN: 2112

Alfa AF: 0.708 Hom.: 5568

Bravo AF: 0.702

Asia WGS AF: 0.795 AC: 2766 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-0.23
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: rs4693602; hg19: chr4-84213619;