19-35064286-T-C

Variant names:

• chr19-35064286-T-C
• rs4806073
• NM_001384133.1:c.812-964T>C

Variant summary

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

The NM_001384133.1(HPN):​c.812-964T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,056 control chromosomes in the GnomAD database, including 56,149 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 0.85 (56149 hom., cov: 30)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPN	NM_001384133.1	c.812-964T>C		intron_variant	Intron 9 of 12	ENST00000672452.2	NP_001371062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPN	ENST00000672452.2	c.812-964T>C		intron_variant	Intron 9 of 12		NM_001384133.1	ENSP00000500664.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129294 AN: 151938 Hom.: 56130 Cov.: 30

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.851 AC: 129356 AN: 152056 Hom.: 56149 Cov.: 30 AF XY: 0.848 AC XY: 63045 AN XY: 74306

African (AFR) AF: 0.668 AC: 27672 AN: 41452

American (AMR) AF: 0.925 AC: 14140 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 3347 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4295 AN: 5116

South Asian (SAS) AF: 0.704 AC: 3389 AN: 4812

European-Finnish (FIN) AF: 0.938 AC: 9929 AN: 10588

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.935 AC: 63571 AN: 68008

Other (OTH) AF: 0.877 AC: 1850 AN: 2110

Alfa AF: 0.910 Hom.: 84667

Bravo AF: 0.849

Asia WGS AF: 0.748 AC: 2603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.29
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: rs4806073; hg19: chr19-35555190;