rs371971762
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001458.5(FLNC):c.4425G>A(p.Ala1475=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,613,498 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A1475A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001458.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.4425G>A | p.Ala1475= | synonymous_variant | 25/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.4425G>A | p.Ala1475= | synonymous_variant | 25/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.4425G>A | p.Ala1475= | synonymous_variant | 25/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.4425G>A | p.Ala1475= | synonymous_variant | 25/47 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152230Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000643 AC: 16AN: 248700Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 135000
GnomAD4 exome AF: 0.000109 AC: 159AN: 1461268Hom.: 0 Cov.: 38 AF XY: 0.000118 AC XY: 86AN XY: 726928
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152230Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74370
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | FLNC: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 12, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 18, 2019 | 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 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at