19-35049978-A-G

Variant names:

• chr19-35049978-A-G
• rs12461158
• NM_001384133.1:c.160+462A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384133.1(HPN):​c.160+462A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,788 control chromosomes in the GnomAD database, including 42,407 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 0.75 (42407 hom., cov: 29)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.98
• Publications: 12 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPN	NM_001384133.1	c.160+462A>G		intron_variant	Intron 4 of 12	ENST00000672452.2	NP_001371062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPN	ENST00000672452.2	c.160+462A>G		intron_variant	Intron 4 of 12		NM_001384133.1	ENSP00000500664.1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113218 AN: 151672 Hom.: 42380 Cov.: 29

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.746 AC: 113293 AN: 151788 Hom.: 42407 Cov.: 29 AF XY: 0.748 AC XY: 55486 AN XY: 74158

African (AFR) AF: 0.704 AC: 29071 AN: 41322

American (AMR) AF: 0.825 AC: 12583 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2880 AN: 3470

East Asian (EAS) AF: 0.852 AC: 4396 AN: 5162

South Asian (SAS) AF: 0.717 AC: 3444 AN: 4806

European-Finnish (FIN) AF: 0.752 AC: 7911 AN: 10518

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50351 AN: 67946

Other (OTH) AF: 0.779 AC: 1642 AN: 2108

Alfa AF: 0.749 Hom.: 80378

Bravo AF: 0.752

Asia WGS AF: 0.764 AC: 2655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.065
DANN	Benign	0.50
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12461158; hg19: chr19-35540882;