rs2305745

chr19-35065377-G-Achr19-35065377-G-Cchr19-35065377-G-T

Variant summary

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

The NM_001384133.1(HPN):c.907+32G>A 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 1,589,612 control chromosomes in the GnomAD database, including 416,185 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 0.63 (32674 hom., cov: 31)
  • Exomes 𝑓: 0.73 (383511 hom.)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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:47041): (HPN antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPN	NM_001384133.1	c.907+32G>A		intron_variant		ENST00000672452.2
HPN-AS1	NR_024562.1	n.405-5599C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPN	ENST00000672452.2	c.907+32G>A		intron_variant			NM_001384133.1	P1
HPN-AS1	ENST00000653822.1	n.213-12258C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96227 AN: 151860 Hom.: 32668 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.677

GnomAD3 exomes AF: 0.702 AC: 171764 AN: 244598 Hom.: 62108 AF XY: 0.697 AC XY: 91993 AN XY: 131966

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.860

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.647

Gnomad SAS exome AF: 0.559

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.736

Gnomad OTH exome AF: 0.736

GnomAD4 exome AF: 0.726 AC: 1043210 AN: 1437634 Hom.: 383511 Cov.: 25 AF XY: 0.721 AC XY: 515419 AN XY: 714956

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.853

Gnomad4 ASJ exome AF: 0.729

Gnomad4 EAS exome AF: 0.698

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.742

Gnomad4 NFE exome AF: 0.746

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.633 AC: 96264 AN: 151978 Hom.: 32674 Cov.: 31 AF XY: 0.636 AC XY: 47237 AN XY: 74290

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.677

Alfa AF: 0.694 Hom.: 8710

Bravo AF: 0.633

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.0060
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2305745; hg19: chr19-35556281;