17-42403241-C-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_012232.6(CAVIN1):c.*1446G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,462 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.045 ( 225 hom., cov: 31)
Exomes 𝑓: 0.076 ( 0 hom. )
Consequence
CAVIN1
NM_012232.6 3_prime_UTR
NM_012232.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.39
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 17-42403241-C-G is Benign according to our data. Variant chr17-42403241-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 323263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0686 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CAVIN1 | NM_012232.6 | c.*1446G>C | 3_prime_UTR_variant | 2/2 | ENST00000357037.6 | NP_036364.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CAVIN1 | ENST00000357037.6 | c.*1446G>C | 3_prime_UTR_variant | 2/2 | 1 | NM_012232.6 | ENSP00000349541 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0446 AC: 6787AN: 152028Hom.: 225 Cov.: 31
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GnomAD4 exome AF: 0.0759 AC: 24AN: 316Hom.: 0 Cov.: 0 AF XY: 0.0748 AC XY: 16AN XY: 214
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GnomAD4 genome AF: 0.0446 AC: 6787AN: 152146Hom.: 225 Cov.: 31 AF XY: 0.0429 AC XY: 3189AN XY: 74392
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Congenital generalized lipodystrophy type 4 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at