rs10029
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1
The ENST00000614113.5(CAV1):c.334C>T(p.Gln112Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,614,128 control chromosomes in the GnomAD database, including 518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.034 ( 295 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 223 hom. )
Consequence
CAV1
ENST00000614113.5 stop_gained
ENST00000614113.5 stop_gained
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.02
Genes affected
CAV1 (HGNC:1527): (caveolin 1) The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade. Caveolin 1 and caveolin 2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. Mutations in this gene have been associated with Berardinelli-Seip congenital lipodystrophy. Alternatively spliced transcripts encode alpha and beta isoforms of caveolin 1.[provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0402 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
BP6
?
Variant 7-116526650-C-T is Benign according to our data. Variant chr7-116526650-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 128610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-116526650-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAV1 | NM_001753.5 | c.156C>T | p.Val52= | synonymous_variant | 2/3 | ENST00000341049.7 | |
CAV1 | NM_001172895.1 | c.63C>T | p.Val21= | synonymous_variant | 2/3 | ||
CAV1 | NM_001172896.2 | c.63C>T | p.Val21= | synonymous_variant | 1/2 | ||
CAV1 | NM_001172897.2 | c.63C>T | p.Val21= | synonymous_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAV1 | ENST00000341049.7 | c.156C>T | p.Val52= | synonymous_variant | 2/3 | 1 | NM_001753.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0341 AC: 5184AN: 152160Hom.: 295 Cov.: 32
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GnomAD3 exomes AF: 0.00890 AC: 2238AN: 251354Hom.: 124 AF XY: 0.00651 AC XY: 884AN XY: 135870
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GnomAD4 exome AF: 0.00345 AC: 5037AN: 1461850Hom.: 223 Cov.: 32 AF XY: 0.00292 AC XY: 2123AN XY: 727220
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GnomAD4 genome ? AF: 0.0341 AC: 5195AN: 152278Hom.: 295 Cov.: 32 AF XY: 0.0327 AC XY: 2435AN XY: 74470
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2015 | 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. - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2022 | 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. - |
Pulmonary hypertension, primary, 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 17, 2023 | - - |
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