rs537998274
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_012232.6(CAVIN1):c.553_570dupGAGCTGGGCGAGGGCGAG(p.Glu190_Arg191insGluLeuGlyGluGlyGlu) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,612,404 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
CAVIN1
NM_012232.6 conservative_inframe_insertion
NM_012232.6 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.02
Genes affected
CAVIN1 (HGNC:9688): (caveolae associated protein 1) This gene encodes a protein that enables the dissociation of paused ternary polymerase I transcription complexes from the 3' end of pre-rRNA transcripts. This protein regulates rRNA transcription by promoting the dissociation of transcription complexes and the reinitiation of polymerase I on nascent rRNA transcripts. This protein also localizes to caveolae at the plasma membrane and is thought to play a critical role in the formation of caveolae and the stabilization of caveolins. This protein translocates from caveolae to the cytoplasm after insulin stimulation. Caveolae contain truncated forms of this protein and may be the site of phosphorylation-dependent proteolysis. This protein is also thought to modify lipid metabolism and insulin-regulated gene expression. Mutations in this gene result in a disorder characterized by generalized lipodystrophy and muscular dystrophy. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00114 (173/152240) while in subpopulation AFR AF= 0.0039 (162/41552). AF 95% confidence interval is 0.00341. There are 1 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CAVIN1 | NM_012232.6 | c.553_570dupGAGCTGGGCGAGGGCGAG | p.Glu190_Arg191insGluLeuGlyGluGlyGlu | conservative_inframe_insertion | 2/2 | ENST00000357037.6 | NP_036364.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CAVIN1 | ENST00000357037.6 | c.553_570dupGAGCTGGGCGAGGGCGAG | p.Glu190_Arg191insGluLeuGlyGluGlyGlu | conservative_inframe_insertion | 2/2 | 1 | NM_012232.6 | ENSP00000349541.4 |
Frequencies
GnomAD3 genomes AF: 0.00112 AC: 171AN: 152122Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000254 AC: 63AN: 247982Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 134330
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GnomAD4 exome AF: 0.000145 AC: 211AN: 1460164Hom.: 0 Cov.: 31 AF XY: 0.000117 AC XY: 85AN XY: 726506
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GnomAD4 genome AF: 0.00114 AC: 173AN: 152240Hom.: 1 Cov.: 32 AF XY: 0.00114 AC XY: 85AN XY: 74434
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University Hospital Muenster | Jan 09, 2023 | ACMG categories: PM2,PM4 - |
Monogenic diabetes Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Feb 12, 2016 | ACMG Criteria: PM4 - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Aug 07, 2023 | - - |
CAVIN1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 15, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at