rs116772523
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000393931.8(JUP):c.1774-13C>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 0.00397 in 1,600,546 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 100 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 114 hom. )
Consequence
JUP
ENST00000393931.8 splice_polypyrimidine_tract, intron
ENST00000393931.8 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.389
Genes affected
JUP (HGNC:6207): (junction plakoglobin) This gene encodes a major cytoplasmic protein which is the only known constituent common to submembranous plaques of both desmosomes and intermediate junctions. This protein forms distinct complexes with cadherins and desmosomal cadherins and is a member of the catenin family since it contains a distinct repeating amino acid motif called the armadillo repeat. Mutation in this gene has been associated with Naxos disease. Alternative splicing occurs in this gene; however, not all transcripts have been fully described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 17-41757797-G-A is Benign according to our data. Variant chr17-41757797-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 36424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41757797-G-A is described in Lovd as [Benign]. Variant chr17-41757797-G-A is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.1774-13C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000393931.8 | NP_002221.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.1774-13C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002230.4 | ENSP00000377508 | P1 | |||
JUP | ENST00000310706.9 | c.1774-13C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | ENSP00000311113 | P1 | ||||
JUP | ENST00000393930.5 | c.1774-13C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | ENSP00000377507 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0216 AC: 3292AN: 152152Hom.: 101 Cov.: 32
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GnomAD3 exomes AF: 0.00553 AC: 1293AN: 233794Hom.: 45 AF XY: 0.00406 AC XY: 515AN XY: 126748
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GnomAD4 exome AF: 0.00212 AC: 3066AN: 1448276Hom.: 114 Cov.: 37 AF XY: 0.00183 AC XY: 1317AN XY: 719100
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GnomAD4 genome AF: 0.0216 AC: 3293AN: 152270Hom.: 100 Cov.: 32 AF XY: 0.0208 AC XY: 1545AN XY: 74448
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:14
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:7
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 17, 2012 | 6.7% (295/4402) of Afr Amer chrom from ESP - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 13, 2023 | - - |
Naxos disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Cardiomyopathy Benign:1
Benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 23, 2022 | - - |
Arrhythmogenic right ventricular dysplasia 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Cardiac arrhythmia Benign:1
Benign, no assertion criteria provided | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 20, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at