19-35059800-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001384133.1(HPN):c.288C>G(p.Leu96=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,570,458 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 9 hom. )

Consequence

HPN
NM_001384133.1 splice_region, synonymous

Scores

Splicing: ADA: 0.009817

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.41

Variant links:

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 links:

HPN-AS1 (HGNC:47041): (HPN antisense RNA 1)

HPN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 19-35059800-C-G is Benign according to our data. Variant chr19-35059800-C-G is described in ClinVar as [Benign]. Clinvar id is 781466.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.41 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (982/152344) while in subpopulation AFR AF= 0.0229 (954/41584). AF 95% confidence interval is 0.0217. There are 13 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPN	NM_001384133.1 linkuse as main transcript	c.288C>G	p.Leu96=	splice_region_variant, synonymous_variant	5/13	ENST00000672452.2
HPN-AS1	NR_024562.1 linkuse as main transcript	n.405-22G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPN	ENST00000672452.2 linkuse as main transcript	c.288C>G	p.Leu96=	splice_region_variant, synonymous_variant	5/13		NM_001384133.1	P1
HPN-AS1	ENST00000653822.1 linkuse as main transcript	n.213-6681G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00644

AC:

981

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.0000294

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00170

AC:

328

AN:

192886

Hom.:

AF XY:

0.00122

AC XY:

126

AN XY:

103384

show subpopulations

Gnomad AFR exome

AF:

0.0242

Gnomad AMR exome

AF:

0.000880

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000880

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000620

GnomAD4 exome

AF:

0.000602

AC:

853

AN:

1418114

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

376

AN XY:

699876

show subpopulations

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.000709

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000100

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000165

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00645

AC:

982

AN:

152344

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

424

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00320

Hom.:

Bravo

AF:

0.00716

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0098

dbscSNV1_RF

Benign

0.19

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over