19-35062437-C-T

Variant names:

• chr19-35062437-C-T
• rs1688043
• NM_001384133.1:c.811+1620C>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.811+1620C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,234 control chromosomes in the GnomAD database, including 62,577 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 0.91 (62577 hom., cov: 31)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPN	NM_001384133.1	c.811+1620C>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.811+1620C>T		intron_variant	Intron 9 of 12		NM_001384133.1	ENSP00000500664.1

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137689 AN: 152116 Hom.: 62542 Cov.: 31

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.914

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

GnomAD4 genome AF: 0.905 AC: 137780 AN: 152234 Hom.: 62577 Cov.: 31 AF XY: 0.904 AC XY: 67274 AN XY: 74456

African (AFR) AF: 0.841 AC: 34910 AN: 41506

American (AMR) AF: 0.943 AC: 14417 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3350 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4494 AN: 5180

South Asian (SAS) AF: 0.813 AC: 3926 AN: 4828

European-Finnish (FIN) AF: 0.937 AC: 9952 AN: 10616

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63636 AN: 68022

Other (OTH) AF: 0.912 AC: 1925 AN: 2110

Alfa AF: 0.923 Hom.: 38943

Bravo AF: 0.906

Asia WGS AF: 0.827 AC: 2877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.23
PhyloP100		-2.4
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: rs1688043; hg19: chr19-35553341;