rs369120591
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001458.5(FLNC):c.366C>T(p.Ile122Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000070 ( 0 hom. )
Consequence
FLNC
NM_001458.5 synonymous
NM_001458.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.00
Genes affected
FLNC (HGNC:3756): (filamin C) This gene encodes one of three related filamin genes, specifically gamma filamin. These filamin proteins crosslink actin filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin cytoskeleton. Three functional domains exist in filamin: an N-terminal filamentous actin-binding domain, a C-terminal self-association domain, and a membrane glycoprotein-binding domain. Mutations in this gene are a cause of cardiopathy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 7-128835339-C-T is Benign according to our data. Variant chr7-128835339-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128835339-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2 with no splicing effect.
BS2
High AC in GnomAdExome4 at 103 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000442 AC: 11AN: 248928Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134922
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GnomAD4 exome AF: 0.0000705 AC: 103AN: 1461434Hom.: 0 Cov.: 32 AF XY: 0.0000825 AC XY: 60AN XY: 727046
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74352
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 30, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 19, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2018 | 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. - |
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 02, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at