rs2305745

Variant names:

• chr19-35065377-G-A
• rs2305745
• NM_001384133.1:c.907+32G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35065377-G-A
• chr19-35065377-G-C
• chr19-35065377-G-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.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
• Publications: 14 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=-0.9).
• 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 rank	MANE	Protein	UniProt
HPN	NM_001384133.1	c.907+32G>A		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.907+32G>A		intron_variant	Intron 10 of 12		NM_001384133.1	ENSP00000500664.1

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

GnomAD2 exomes AF: 0.702 AC: 171764 AN: 244598 AF XY: 0.697

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 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

African (AFR) AF: 0.361 AC: 11876 AN: 32938

American (AMR) AF: 0.853 AC: 37599 AN: 44104

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 18571 AN: 25466

East Asian (EAS) AF: 0.698 AC: 27534 AN: 39458

South Asian (SAS) AF: 0.561 AC: 47603 AN: 84826

European-Finnish (FIN) AF: 0.742 AC: 39469 AN: 53176

Middle Eastern (MID) AF: 0.698 AC: 3985 AN: 5708

European-Non Finnish (NFE) AF: 0.746 AC: 814639 AN: 1092522

Other (OTH) AF: 0.706 AC: 41934 AN: 59436

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

African (AFR) AF: 0.373 AC: 15469 AN: 41424

American (AMR) AF: 0.777 AC: 11870 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2559 AN: 3468

East Asian (EAS) AF: 0.652 AC: 3348 AN: 5138

South Asian (SAS) AF: 0.544 AC: 2621 AN: 4818

European-Finnish (FIN) AF: 0.750 AC: 7946 AN: 10592

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50033 AN: 67958

Other (OTH) AF: 0.677 AC: 1427 AN: 2108

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
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2305745; hg19: chr19-35556281;