4-83292466-A-G

Position:

• chr4-83292466-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.*2878T>C		3_prime_UTR_variant	12/12	ENST00000311412.10	NP_001092010.1
HPSE	NM_006665.6	c.*2878T>C		3_prime_UTR_variant	13/13		NP_006656.2
HPSE	NM_001199830.1	c.*2878T>C		3_prime_UTR_variant	11/11		NP_001186759.1
HPSE	NM_001166498.3	c.*2878T>C		3_prime_UTR_variant	11/11		NP_001159970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412	c.*2878T>C		3_prime_UTR_variant	12/12	1	NM_001098540.3	ENSP00000308107.5
HPSE	ENST00000405413	c.*2878T>C		3_prime_UTR_variant	13/13	1		ENSP00000384262.2

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

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

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.707

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4693602; hg19: chr4-84213619;