chr4-83322396-A-G

Variant names:

• chr4-83322396-A-G
• rs4328905
• NM_001098540.3:c.228-32T>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.228-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,570,638 control chromosomes in the GnomAD database, including 20,075 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 0.18 (3151 hom., cov: 30)
  • Exomes 𝑓: 0.14 (16924 hom.)
• Consequence: HPSE NM_001098540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.228-32T>C		intron_variant	Intron 1 of 11	ENST00000311412.10	NP_001092010.1
HPSE	NM_006665.6	c.228-32T>C		intron_variant	Intron 2 of 12		NP_006656.2
HPSE	NM_001199830.1	c.228-32T>C		intron_variant	Intron 1 of 10		NP_001186759.1
HPSE	NM_001166498.3	c.228-32T>C		intron_variant	Intron 2 of 10		NP_001159970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.228-32T>C		intron_variant	Intron 1 of 11	1	NM_001098540.3	ENSP00000308107.5

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27755 AN: 151876 Hom.: 3146 Cov.: 30

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.0798

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.172

GnomAD2 exomes AF: 0.181 AC: 39142 AN: 215812 AF XY: 0.178

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.422

Gnomad FIN exome AF: 0.0823

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.139 AC: 197861 AN: 1418644 Hom.: 16924 Cov.: 26 AF XY: 0.142 AC XY: 99707 AN XY: 704030

African (AFR) AF: 0.293 AC: 9273 AN: 31652

American (AMR) AF: 0.216 AC: 7942 AN: 36808

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3212 AN: 24574

East Asian (EAS) AF: 0.406 AC: 15840 AN: 39038

South Asian (SAS) AF: 0.246 AC: 19680 AN: 79996

European-Finnish (FIN) AF: 0.0798 AC: 4193 AN: 52512

Middle Eastern (MID) AF: 0.198 AC: 1113 AN: 5620

European-Non Finnish (NFE) AF: 0.117 AC: 127385 AN: 1089796

Other (OTH) AF: 0.157 AC: 9223 AN: 58648

GnomAD4 genome AF: 0.183 AC: 27777 AN: 151994 Hom.: 3151 Cov.: 30 AF XY: 0.184 AC XY: 13698 AN XY: 74284

African (AFR) AF: 0.279 AC: 11568 AN: 41424

American (AMR) AF: 0.193 AC: 2948 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3466

East Asian (EAS) AF: 0.424 AC: 2188 AN: 5162

South Asian (SAS) AF: 0.260 AC: 1253 AN: 4818

European-Finnish (FIN) AF: 0.0798 AC: 843 AN: 10564

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7979 AN: 67956

Other (OTH) AF: 0.174 AC: 367 AN: 2110

Alfa AF: 0.144 Hom.: 5060

Bravo AF: 0.196

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.43
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4328905; hg19: chr4-84243549; COSMIC: COSV60986649;