rs201966419
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BP6BS1
The NM_001753.5(CAV1):āc.500T>Cā(p.Phe167Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000146 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 32)
Exomes š: 0.00015 ( 0 hom. )
Consequence
CAV1
NM_001753.5 missense
NM_001753.5 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 5.88
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 Likely_benign. Variant got -4 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.791
BP6
?
Variant 7-116559250-T-C is Benign according to our data. Variant chr7-116559250-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 541324.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000105 (16/152310) while in subpopulation NFE AF= 0.000162 (11/68026). AF 95% confidence interval is 0.0000905. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAV1 | NM_001753.5 | c.500T>C | p.Phe167Ser | missense_variant | 3/3 | ENST00000341049.7 | |
CAV1 | NM_001172895.1 | c.407T>C | p.Phe136Ser | missense_variant | 3/3 | ||
CAV1 | NM_001172896.2 | c.407T>C | p.Phe136Ser | missense_variant | 2/2 | ||
CAV1 | NM_001172897.2 | c.407T>C | p.Phe136Ser | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAV1 | ENST00000341049.7 | c.500T>C | p.Phe167Ser | missense_variant | 3/3 | 1 | NM_001753.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000838 AC: 21AN: 250712Hom.: 0 AF XY: 0.0000886 AC XY: 12AN XY: 135494
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GnomAD4 exome AF: 0.000150 AC: 219AN: 1461482Hom.: 0 Cov.: 32 AF XY: 0.000125 AC XY: 91AN XY: 727052
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74484
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Monogenic diabetes Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Feb 22, 2019 | ACMG criteria: PP3 (REVEL 0.9 + 10 predictors) = VUS - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2023 | Reported as c.407 T>C p.(Phe136Ser) due to use of alternate nomenclature in individuals with pulmonary arterial hypertension (Zhu et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33264630, 32041611, 31727138) - |
Pulmonary hypertension, primary, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;T;.;.
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;.;D;D;D;D
Sift4G
Uncertain
T;T;T;T;D;T;T
Polyphen
D;.;.;.;.;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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