rs41523449

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.355
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
HPNNM_001384133.1 linkc.17-2488G>A intron_variant ENST00000672452.2 NP_001371062.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HPNENST00000672452.2 linkc.17-2488G>A intron_variant NM_001384133.1 ENSP00000500664.1 P05981

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41523449; hg19: chr19-35537706; API