rs2305747

Variant names:

• chr19-35065453-C-T
• rs2305747
• NM_001384133.1:c.908-86C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HPN	NM_001384133.1	c.908-86C>T		intron_variant	Intron 10 of 12	ENST00000672452.2	NP_001371062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPN	ENST00000672452.2	c.908-86C>T		intron_variant	Intron 10 of 12		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

African (AFR) AF: 0.366 AC: 11868 AN: 32418

American (AMR) AF: 0.851 AC: 33979 AN: 39948

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 17630 AN: 24212

East Asian (EAS) AF: 0.699 AC: 27316 AN: 39062

South Asian (SAS) AF: 0.563 AC: 46084 AN: 81926

European-Finnish (FIN) AF: 0.742 AC: 38415 AN: 51768

Middle Eastern (MID) AF: 0.698 AC: 3928 AN: 5624

European-Non Finnish (NFE) AF: 0.746 AC: 803717 AN: 1077876

Other (OTH) AF: 0.705 AC: 41239 AN: 58474

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

African (AFR) AF: 0.378 AC: 15618 AN: 41324

American (AMR) AF: 0.778 AC: 11885 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2560 AN: 3468

East Asian (EAS) AF: 0.652 AC: 3346 AN: 5128

South Asian (SAS) AF: 0.546 AC: 2628 AN: 4812

European-Finnish (FIN) AF: 0.751 AC: 7923 AN: 10554

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50029 AN: 67920

Other (OTH) AF: 0.678 AC: 1430 AN: 2108

Alfa AF: 0.711 Hom.: 49735

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
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2305747; hg19: chr19-35556357;