rs2305747

Positions:

• chr19-35065453-C-T

Variant summary

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

The NM_001384133.1(HPN):​c.908-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,563,096 control chromosomes in the GnomAD database, including 409,062 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 0.64 (32759 hom., cov: 30)
  • Exomes 𝑓: 0.73 (376303 hom.)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

Genes affected

HPN (HGNC:5155): (hepsin) This gene encodes a type II transmembrane serine protease that may be involved in diverse cellular functions, including blood coagulation and the maintenance of cell morphology. Expression of the encoded protein is associated with the growth and progression of cancers, particularly prostate cancer. The protein is cleaved into a catalytic serine protease chain and a non-catalytic scavenger receptor cysteine-rich chain, which associate via a single disulfide bond. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

HPN-AS1 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPN	NM_001384133.1	c.908-86C>T		intron_variant		ENST00000672452.2	NP_001371062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPN	ENST00000672452.2	c.908-86C>T		intron_variant			NM_001384133.1	ENSP00000500664.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96372 AN: 151670 Hom.: 32751 Cov.: 30

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.679

GnomAD4 exome AF: 0.726 AC: 1024176 AN: 1411308 Hom.: 376303 Cov.: 24 AF XY: 0.721 AC XY: 505464 AN XY: 700980

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.851

Gnomad4 ASJ exome AF: 0.728

Gnomad4 EAS exome AF: 0.699

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.742

Gnomad4 NFE exome AF: 0.746

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.635 AC: 96411 AN: 151788 Hom.: 32759 Cov.: 30 AF XY: 0.638 AC XY: 47311 AN XY: 74172

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.678

Alfa AF: 0.725 Hom.: 39111

Bravo AF: 0.634

Asia WGS AF: 0.599 AC: 2082 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	1.1
DANN	Benign	0.51

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: rs2305747; hg19: chr19-35556357;