rs2451996

chr19-35054059-G-Achr19-35054059-G-C

Variant summary

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

The NM_001384133.1(HPN):c.160+4543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,128 control chromosomes in the GnomAD database, including 21,273 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 0.50 (21273 hom., cov: 32)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPN	NM_001384133.1	c.160+4543G>A		intron_variant		ENST00000672452.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPN	ENST00000672452.2	c.160+4543G>A		intron_variant			NM_001384133.1	P1
HPN-AS1	ENST00000653822.1	n.213-940C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76793 AN: 152010 Hom.: 21263 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.505 AC: 76821 AN: 152128 Hom.: 21273 Cov.: 32 AF XY: 0.510 AC XY: 37920 AN XY: 74374

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.567

Alfa AF: 0.542 Hom.: 12689

Bravo AF: 0.509

Asia WGS AF: 0.547 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.21
Dann	Benign	0.72

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: rs2451996; hg19: chr19-35544963;