rs765545958
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001458.5(FLNC):c.969+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,555,968 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 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000071 ( 0 hom. )
Consequence
FLNC
NM_001458.5 intron
NM_001458.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.15
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 7-128837769-G-A is Benign according to our data. Variant chr7-128837769-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1630490.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.969+14G>A | intron_variant | ENST00000325888.13 | |||
FLNC | NM_001127487.2 | c.969+14G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.969+14G>A | intron_variant | 1 | NM_001458.5 | P3 | |||
FLNC | ENST00000346177.6 | c.969+14G>A | intron_variant | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000122 AC: 2AN: 163944Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 88672
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GnomAD4 exome AF: 0.00000712 AC: 10AN: 1403726Hom.: 0 Cov.: 33 AF XY: 0.00000288 AC XY: 2AN XY: 694588
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
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 09, 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