rs2305749

Positions:

• chr19-35041401-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000262626.6(HPN):​c.-785-321T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,308 control chromosomes in the GnomAD database, including 17,074 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 0.47 (17074 hom., cov: 31)
• Consequence: HPN ENST00000262626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPN	NM_002151.5	c.-205-321T>G		intron_variant
HPN	NM_182983.5	c.-785-321T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPN	ENST00000262626.6	c.-785-321T>G		intron_variant		1		P1
HPN	ENST00000392226.5	c.-205-321T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 70941 AN: 151190 Hom.: 17044 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.469 AC: 71017 AN: 151308 Hom.: 17074 Cov.: 31 AF XY: 0.468 AC XY: 34586 AN XY: 73922

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.519

Alfa AF: 0.460 Hom.: 2035

Bravo AF: 0.475

Asia WGS AF: 0.413 AC: 1433 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs2305749; hg19: chr19-35532305;