rs6856901

Positions:

• chr4-83295215-C-G
• chr4-83295215-C-T

Variant summary

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

The NM_001098540.3(HPSE):​c.*129G>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 0.254 in 644,462 control chromosomes in the GnomAD database, including 21,954 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 0.27 (5837 hom., cov: 32)
  • Exomes 𝑓: 0.25 (16117 hom.)
• Consequence: HPSE NM_001098540.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.*129G>C		3_prime_UTR_variant	12/12	ENST00000311412.10	NP_001092010.1
HPSE	NM_001166498.3	c.*129G>C		3_prime_UTR_variant	11/11		NP_001159970.1
HPSE	NM_001199830.1	c.*129G>C		3_prime_UTR_variant	11/11		NP_001186759.1
HPSE	NM_006665.6	c.*129G>C		3_prime_UTR_variant	13/13		NP_006656.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.*129G>C		3_prime_UTR_variant	12/12	1	NM_001098540.3	ENSP00000308107	P1
HPSE	ENST00000405413.6	c.*129G>C		3_prime_UTR_variant	13/13	1		ENSP00000384262	P1
HPSE	ENST00000681769.1	c.1473-1620G>C		intron_variant				ENSP00000506434

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41211 AN: 151810 Hom.: 5822 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.248 AC: 122110 AN: 492534 Hom.: 16117 Cov.: 7 AF XY: 0.246 AC XY: 63763 AN XY: 258804

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.272 AC: 41265 AN: 151928 Hom.: 5837 Cov.: 32 AF XY: 0.267 AC XY: 19842 AN XY: 74288

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.265

Alfa AF: 0.123 Hom.: 208

Bravo AF: 0.286

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.25
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: rs6856901; hg19: chr4-84216368; COSMIC: COSV60986596; COSMIC: COSV60986596;