19-35063068-C-T

Variant names:

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

Variant summary

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

The NM_001384133.1(HPN):​c.812-2182C>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
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384133.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPN	NM_001384133.1	MANE Select	c.812-2182C>T		intron	N/A	NP_001371062.1	P05981
	HPN	NM_001375441.3		c.812-2182C>T		intron	N/A	NP_001362370.1	A0A140VJK9
	HPN	NM_002151.5		c.812-2182C>T		intron	N/A	NP_002142.1	P05981

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPN	ENST00000672452.2	MANE Select	c.812-2182C>T		intron	N/A	ENSP00000500664.1	P05981
	HPN	ENST00000262626.6	TSL:1	c.812-2182C>T		intron	N/A	ENSP00000262626.2	P05981
	HPN	ENST00000392226.5	TSL:1	c.812-2182C>T		intron	N/A	ENSP00000376060.1	P05981

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

African (AFR) AF: 0.668 AC: 27684 AN: 41422

American (AMR) AF: 0.925 AC: 14160 AN: 15306

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

East Asian (EAS) AF: 0.842 AC: 4363 AN: 5184

South Asian (SAS) AF: 0.704 AC: 3396 AN: 4822

European-Finnish (FIN) AF: 0.937 AC: 9957 AN: 10622

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

European-Non Finnish (NFE) AF: 0.935 AC: 63570 AN: 68010

Other (OTH) AF: 0.877 AC: 1854 AN: 2114

Alfa AF: 0.860 Hom.: 8406

Bravo AF: 0.849

Asia WGS AF: 0.748 AC: 2602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		-0.53
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: rs1350290; hg19: chr19-35553972;