chr4-83319694-T-C

Position:

• chr4-83319694-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098540.3(HPSE):​c.374-225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,052 control chromosomes in the GnomAD database, including 48,241 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 (48241 hom., cov: 30)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.374-225A>G		intron_variant		ENST00000311412.10	NP_001092010.1
HPSE	NM_001166498.3	c.374-225A>G		intron_variant			NP_001159970.1
HPSE	NM_001199830.1	c.374-225A>G		intron_variant			NP_001186759.1
HPSE	NM_006665.6	c.374-225A>G		intron_variant			NP_006656.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.374-225A>G		intron_variant		1	NM_001098540.3	ENSP00000308107	P1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120847 AN: 151934 Hom.: 48206 Cov.: 30

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.795 AC: 120935 AN: 152052 Hom.: 48241 Cov.: 30 AF XY: 0.794 AC XY: 58988 AN XY: 74318

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.781

Alfa AF: 0.775 Hom.: 7388

Bravo AF: 0.795

Asia WGS AF: 0.849 AC: 2952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.70

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: rs11099594; hg19: chr4-84240847;