7-142752857-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBS1BS2_Supporting
The NM_002769.5(PRSS1):c.592-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,613,664 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0021 ( 2 hom., cov: 41)
Exomes 𝑓: 0.0026 ( 36 hom. )
Consequence
PRSS1
NM_002769.5 splice_polypyrimidine_tract, intron
NM_002769.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00003634
2
Clinical Significance
Conservation
PhyloP100: 0.532
Genes affected
PRSS1 (HGNC:9475): (serine protease 1) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 7-142752857-C-T is Benign according to our data. Variant chr7-142752857-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-142752857-C-T is described in Lovd as [Benign]. Variant chr7-142752857-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00264 (3864/1461332) while in subpopulation MID AF= 0.0339 (195/5758). AF 95% confidence interval is 0.03. There are 36 homozygotes in gnomad4_exome. There are 2326 alleles in male gnomad4_exome subpopulation. Median coverage is 47. This position pass quality control queck.
BS2
High AC in GnomAd4 at 314 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRSS1 | NM_002769.5 | c.592-11C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000311737.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRSS1 | ENST00000311737.12 | c.592-11C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002769.5 | P1 | |||
PRSS1 | ENST00000486171.5 | c.634-11C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
PRSS1 | ENST00000492062.1 | c.425-11C>T | splice_polypyrimidine_tract_variant, intron_variant | 2 | |||||
PRSS1 | ENST00000463701.1 | n.1056-11C>T | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00206 AC: 314AN: 152214Hom.: 2 Cov.: 41
GnomAD3 genomes
AF:
AC:
314
AN:
152214
Hom.:
Cov.:
41
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00356 AC: 894AN: 251458Hom.: 2 AF XY: 0.00445 AC XY: 605AN XY: 135898
GnomAD3 exomes
AF:
AC:
894
AN:
251458
Hom.:
AF XY:
AC XY:
605
AN XY:
135898
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00264 AC: 3864AN: 1461332Hom.: 36 Cov.: 47 AF XY: 0.00320 AC XY: 2326AN XY: 727002
GnomAD4 exome
AF:
AC:
3864
AN:
1461332
Hom.:
Cov.:
47
AF XY:
AC XY:
2326
AN XY:
727002
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00206 AC: 314AN: 152332Hom.: 2 Cov.: 41 AF XY: 0.00213 AC XY: 159AN XY: 74490
GnomAD4 genome
AF:
AC:
314
AN:
152332
Hom.:
Cov.:
41
AF XY:
AC XY:
159
AN XY:
74490
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Asia WGS
AF:
AC:
18
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary pancreatitis Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 01, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2015 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 04, 2020 | This variant is associated with the following publications: (PMID: 27264265, 24458023, 30134826, 28502372) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at