rs7405731
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002230.4(JUP):c.213T>C(p.Asp71Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,606,858 control chromosomes in the GnomAD database, including 458,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_002230.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- arrhythmogenic right ventricular dysplasia 12Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- inherited epidermolysis bullosaInheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
- Naxos diseaseInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
- lethal acantholytic epidermolysis bullosaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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JUP | NM_002230.4 | c.213T>C | p.Asp71Asp | synonymous_variant | Exon 3 of 14 | ENST00000393931.8 | NP_002221.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.771 AC: 117207AN: 152052Hom.: 45801 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.711 AC: 167306AN: 235266 AF XY: 0.721 show subpopulations
GnomAD4 exome AF: 0.750 AC: 1091432AN: 1454688Hom.: 412516 Cov.: 63 AF XY: 0.752 AC XY: 543348AN XY: 722944 show subpopulations
GnomAD4 genome AF: 0.771 AC: 117318AN: 152170Hom.: 45851 Cov.: 32 AF XY: 0.762 AC XY: 56711AN XY: 74376 show subpopulations
ClinVar
Submissions by phenotype
not specified Benign:8
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Naxos disease Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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Arrhythmogenic right ventricular dysplasia 12 Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not provided Benign:2
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Cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as 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. -
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at