rs41523449

Variant names:

• chr19-35046802-G-A
• rs41523449
• NM_001384133.1:c.17-2488G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.81).
• 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 rank	MANE	Protein	UniProt
HPN	NM_001384133.1	c.17-2488G>A		intron_variant	Intron 2 of 12	ENST00000672452.2	NP_001371062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPN	ENST00000672452.2	c.17-2488G>A		intron_variant	Intron 2 of 12		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

African (AFR) AF: 0.0273 AC: 1135 AN: 41552

American (AMR) AF: 0.0799 AC: 1222 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3472

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5178

South Asian (SAS) AF: 0.0774 AC: 373 AN: 4818

European-Finnish (FIN) AF: 0.163 AC: 1722 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10621 AN: 67992

Other (OTH) AF: 0.0939 AC: 198 AN: 2108

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
PhyloP100		0.35
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: rs41523449; hg19: chr19-35537706;