rs41523449

Positions:

• chr19-35046802-G-A

Variant summary

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

The NM_001384133.1(HPN):​c.17-2488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,208 control chromosomes in the GnomAD database, including 1,103 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 0.10 (1103 hom., cov: 32)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPN	NM_001384133.1	c.17-2488G>A		intron_variant		ENST00000672452.2	NP_001371062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPN	ENST00000672452.2	c.17-2488G>A		intron_variant			NM_001384133.1	ENSP00000500664.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15840 AN: 152090 Hom.: 1103 Cov.: 32

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.0944

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15839 AN: 152208 Hom.: 1103 Cov.: 32 AF XY: 0.103 AC XY: 7640 AN XY: 74420

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.0799

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.0774

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.0939

Alfa AF: 0.124 Hom.: 174

Bravo AF: 0.0960

Asia WGS AF: 0.0510 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.81

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: rs41523449; hg19: chr19-35537706;