rs200717144
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001458.5(FLNC):c.3960G>A(p.Glu1320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,613,978 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 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
FLNC
NM_001458.5 synonymous
NM_001458.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.182
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 7-128846159-G-A is Benign according to our data. Variant chr7-128846159-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 472051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.182 with no splicing effect.
BS2
?
High AC in GnomAd4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.3960G>A | p.Glu1320= | synonymous_variant | 22/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.3960G>A | p.Glu1320= | synonymous_variant | 22/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3960G>A | p.Glu1320= | synonymous_variant | 22/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.3960G>A | p.Glu1320= | synonymous_variant | 22/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000241 AC: 60AN: 248840Hom.: 0 AF XY: 0.000244 AC XY: 33AN XY: 135124
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GnomAD4 exome AF: 0.000141 AC: 206AN: 1461768Hom.: 0 Cov.: 34 AF XY: 0.000158 AC XY: 115AN XY: 727190
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | FLNC: BP4, BP7 - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2020 | 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 | Invitae | Jan 29, 2024 | - - |
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