rs116974302
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000325888.13(FLNC):c.6120C>T(p.Asp2040=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,613,570 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00062 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00054 ( 7 hom. )
Consequence
FLNC
ENST00000325888.13 synonymous
ENST00000325888.13 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.63
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 7-128852943-C-T is Benign according to our data. Variant chr7-128852943-C-T is described in ClinVar as [Benign]. Clinvar id is 383328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128852943-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.63 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000624 (95/152270) while in subpopulation EAS AF= 0.016 (83/5176). AF 95% confidence interval is 0.0133. There are 1 homozygotes in gnomad4. There are 62 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 95 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.6120C>T | p.Asp2040= | synonymous_variant | 37/48 | ENST00000325888.13 | NP_001449.3 | |
FLNC-AS1 | NR_149055.1 | n.215+342G>A | intron_variant, non_coding_transcript_variant | |||||
FLNC | NM_001127487.2 | c.6021C>T | p.Asp2007= | synonymous_variant | 36/47 | NP_001120959.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.6120C>T | p.Asp2040= | synonymous_variant | 37/48 | 1 | NM_001458.5 | ENSP00000327145 | P3 | |
FLNC | ENST00000346177.6 | c.6021C>T | p.Asp2007= | synonymous_variant | 36/47 | 1 | ENSP00000344002 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.215+342G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000624 AC: 95AN: 152152Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00132 AC: 329AN: 249350Hom.: 1 AF XY: 0.00118 AC XY: 160AN XY: 135360
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GnomAD4 exome AF: 0.000535 AC: 782AN: 1461300Hom.: 7 Cov.: 33 AF XY: 0.000541 AC XY: 393AN XY: 726956
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GnomAD4 genome AF: 0.000624 AC: 95AN: 152270Hom.: 1 Cov.: 33 AF XY: 0.000833 AC XY: 62AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 20, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2016 | 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. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 09, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2019 | This alteration is classified as 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
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | 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