19-35049978-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• 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/exons	MANE	UniProt
HPN	NM_001384133.1	c.160+462A>G		intron_variant		ENST00000672452.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPN	ENST00000672452.2	c.160+462A>G		intron_variant			NM_001384133.1	P1
HPN-AS1	ENST00000653822.1	n.306+3048T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.779

Alfa AF: 0.749 Hom.: 58895

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12461158; hg19: chr19-35540882;