19-35066536-C-T

Variant names:

• chr19-35066536-C-T
• rs1688029
• NM_001384133.1:c.*249C>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.*249C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 547,850 control chromosomes in the GnomAD database, including 120,683 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 0.58 (28520 hom., cov: 30)
  • Exomes 𝑓: 0.68 (92163 hom.)
• Consequence: HPN NM_001384133.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.712 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.*249C>T		3_prime_UTR	Exon 13 of 13	NP_001371062.1	P05981
	HPN	NM_001375441.3		c.*249C>T		3_prime_UTR	Exon 13 of 13	NP_001362370.1	A0A140VJK9
	HPN	NM_002151.5		c.*249C>T		3_prime_UTR	Exon 14 of 14	NP_002142.1	P05981

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPN	ENST00000672452.2	MANE Select	c.*249C>T		3_prime_UTR	Exon 13 of 13	ENSP00000500664.1	P05981
	HPN	ENST00000262626.6	TSL:1	c.*249C>T		3_prime_UTR	Exon 13 of 13	ENSP00000262626.2	P05981
	HPN	ENST00000392226.5	TSL:1	c.*249C>T		3_prime_UTR	Exon 14 of 14	ENSP00000376060.1	P05981

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88772 AN: 151742 Hom.: 28517 Cov.: 30

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.676 AC: 267797 AN: 395990 Hom.: 92163 Cov.: 4 AF XY: 0.672 AC XY: 138047 AN XY: 205292

African (AFR) AF: 0.305 AC: 3517 AN: 11524

American (AMR) AF: 0.739 AC: 11626 AN: 15732

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 9735 AN: 12684

East Asian (EAS) AF: 0.725 AC: 21081 AN: 29058

South Asian (SAS) AF: 0.548 AC: 17776 AN: 32462

European-Finnish (FIN) AF: 0.686 AC: 18865 AN: 27502

Middle Eastern (MID) AF: 0.717 AC: 1273 AN: 1776

European-Non Finnish (NFE) AF: 0.695 AC: 168053 AN: 241742

Other (OTH) AF: 0.675 AC: 15871 AN: 23510

GnomAD4 genome AF: 0.585 AC: 88787 AN: 151860 Hom.: 28520 Cov.: 30 AF XY: 0.588 AC XY: 43645 AN XY: 74228

African (AFR) AF: 0.296 AC: 12239 AN: 41376

American (AMR) AF: 0.723 AC: 11044 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2688 AN: 3466

East Asian (EAS) AF: 0.700 AC: 3605 AN: 5152

South Asian (SAS) AF: 0.531 AC: 2550 AN: 4798

European-Finnish (FIN) AF: 0.689 AC: 7276 AN: 10562

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47014 AN: 67922

Other (OTH) AF: 0.665 AC: 1406 AN: 2114

Alfa AF: 0.662 Hom.: 144854

Bravo AF: 0.579

Asia WGS AF: 0.596 AC: 2071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.63
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1688029; hg19: chr19-35557440;