19-35063068-C-T

Variant names:

• chr19-35063068-C-T
• rs1350290
• NM_001384133.1:c.812-2182C>T

Variant summary

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

The NM_001384133.1(HPN):​c.812-2182C>T 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 152,158 control chromosomes in the GnomAD database, including 56,208 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 (56208 hom., cov: 32)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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=-0.8).
• 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.812-2182C>T		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.812-2182C>T		intron_variant	Intron 9 of 12		NM_001384133.1	ENSP00000500664.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129432 AN: 152040 Hom.: 56189 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.851 AC: 129494 AN: 152158 Hom.: 56208 Cov.: 32 AF XY: 0.849 AC XY: 63166 AN XY: 74424

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.925

Gnomad4 ASJ AF: 0.964

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.935

Gnomad4 OTH AF: 0.877

Alfa AF: 0.866 Hom.: 8228

Bravo AF: 0.849

Asia WGS AF: 0.748 AC: 2602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.83

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: rs1350290; hg19: chr19-35553972;