Menu
GeneBe

19-35060720-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001384133.1(HPN):c.714C>T(p.Val238=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,614,170 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0033 ( 17 hom. )

Consequence

HPN
NM_001384133.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.80
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-AS1 (HGNC:47041): (HPN antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-35060720-C-T is Benign according to our data. Variant chr19-35060720-C-T is described in ClinVar as [Benign]. Clinvar id is 787571.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.8 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HPNNM_001384133.1 linkuse as main transcriptc.714C>T p.Val238= synonymous_variant 9/13 ENST00000672452.2
HPN-AS1NR_024562.1 linkuse as main transcriptn.405-942G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HPNENST00000672452.2 linkuse as main transcriptc.714C>T p.Val238= synonymous_variant 9/13 NM_001384133.1 P1
HPN-AS1ENST00000653822.1 linkuse as main transcriptn.213-7601G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00264
AC:
402
AN:
152252
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000892
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00530
Gnomad ASJ
AF:
0.00692
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000376
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00359
Gnomad OTH
AF:
0.00573
GnomAD3 exomes
AF:
0.00314
AC:
788
AN:
250954
Hom.:
6
AF XY:
0.00277
AC XY:
376
AN XY:
135596
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.00810
Gnomad ASJ exome
AF:
0.00637
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.00310
Gnomad OTH exome
AF:
0.0118
GnomAD4 exome
AF:
0.00328
AC:
4790
AN:
1461800
Hom.:
17
Cov.:
34
AF XY:
0.00313
AC XY:
2277
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.00767
Gnomad4 ASJ exome
AF:
0.00605
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000431
Gnomad4 NFE exome
AF:
0.00364
Gnomad4 OTH exome
AF:
0.00336
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00264
AC:
402
AN:
152370
Hom.:
0
Cov.:
33
AF XY:
0.00243
AC XY:
181
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.000890
Gnomad4 AMR
AF:
0.00529
Gnomad4 ASJ
AF:
0.00692
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000376
Gnomad4 NFE
AF:
0.00359
Gnomad4 OTH
AF:
0.00567
Alfa
AF:
0.00329
Hom.:
0
Bravo
AF:
0.00319
Asia WGS
AF:
0.000289
AC:
2
AN:
3478
EpiCase
AF:
0.00414
EpiControl
AF:
0.00373

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 submitterclinical testingInvitaeMay 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
13
Dann
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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.

Other links and lift over

dbSNP: rs12981585; hg19: chr19-35551624; COSMIC: COSV52883362; COSMIC: COSV52883362; API