rs10410046

Variant names:

• chr19-35040898-G-A
• rs10410046
• ENST00000262626.6:c.-786+353G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000262626.6(HPN):​c.-786+353G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 152,314 control chromosomes in the GnomAD database, including 14 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 0.0066 (14 hom., cov: 33)
• Consequence: HPN ENST00000262626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 1 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=-0.71).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00662 (1009/152314) while in subpopulation AFR AF = 0.0231 (962/41570). AF 95% confidence interval is 0.0219. There are 14 homozygotes in GnomAd4. There are 498 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262626.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPN	NM_002151.5		c.-206+353G>A		intron	N/A	NP_002142.1
	HPN	NM_182983.5		c.-786+353G>A		intron	N/A	NP_892028.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPN	ENST00000262626.6	TSL:1	c.-786+353G>A		intron	N/A	ENSP00000262626.2
	HPN	ENST00000392226.5	TSL:1	c.-206+353G>A		intron	N/A	ENSP00000376060.1
	HPN-AS1	ENST00000796454.1		n.413-12340C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00663 AC: 1009 AN: 152196 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00662 AC: 1009 AN: 152314 Hom.: 14 Cov.: 33 AF XY: 0.00669 AC XY: 498 AN XY: 74474

African (AFR) AF: 0.0231 AC: 962 AN: 41570

American (AMR) AF: 0.00261 AC: 40 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00778 Hom.: 0

Bravo AF: 0.00747

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.89
PhyloP100		0.38
PromoterAI		-0.15	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10410046; hg19: chr19-35531802;