rs2451996

Variant names:

• chr19-35054059-G-A
• rs2451996
• NM_001384133.1:c.160+4543G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35054059-G-A
• chr19-35054059-G-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.160+4543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,128 control chromosomes in the GnomAD database, including 21,273 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 0.50 (21273 hom., cov: 32)
• Consequence: HPN NM_001384133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.675 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.160+4543G>A		intron	N/A	NP_001371062.1
	HPN	NM_001375441.3		c.160+4543G>A		intron	N/A	NP_001362370.1
	HPN	NM_002151.5		c.160+4543G>A		intron	N/A	NP_002142.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPN	ENST00000672452.2	MANE Select	c.160+4543G>A		intron	N/A	ENSP00000500664.1
	HPN	ENST00000262626.6	TSL:1	c.160+4543G>A		intron	N/A	ENSP00000262626.2
	HPN	ENST00000392226.5	TSL:1	c.160+4543G>A		intron	N/A	ENSP00000376060.1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76793 AN: 152010 Hom.: 21263 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.505 AC: 76821 AN: 152128 Hom.: 21273 Cov.: 32 AF XY: 0.510 AC XY: 37920 AN XY: 74374

African (AFR) AF: 0.267 AC: 11057 AN: 41486

American (AMR) AF: 0.686 AC: 10488 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2157 AN: 3464

East Asian (EAS) AF: 0.654 AC: 3381 AN: 5170

South Asian (SAS) AF: 0.454 AC: 2185 AN: 4818

European-Finnish (FIN) AF: 0.591 AC: 6264 AN: 10596

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39237 AN: 67988

Other (OTH) AF: 0.567 AC: 1198 AN: 2114

Alfa AF: 0.541 Hom.: 13922

Bravo AF: 0.509

Asia WGS AF: 0.547 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.72
PhyloP100		-0.64
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: rs2451996; hg19: chr19-35544963;