chr7-128856760-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BP6BS2
The NM_001458.5(FLNC):c.7400G>A(p.Arg2467His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2467C) has been classified as Likely benign.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.7400G>A | p.Arg2467His | missense_variant | 45/48 | ENST00000325888.13 | |
FLNC-AS1 | NR_149055.1 | n.103-3363C>T | intron_variant, non_coding_transcript_variant | ||||
FLNC | NM_001127487.2 | c.7301G>A | p.Arg2434His | missense_variant | 44/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.7400G>A | p.Arg2467His | missense_variant | 45/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.7301G>A | p.Arg2434His | missense_variant | 44/47 | 1 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.103-3363C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249796Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135400
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 727238
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2022 | The p.R2467H variant (also known as c.7400G>A), located in coding exon 45 of the FLNC gene, results from a G to A substitution at nucleotide position 7400. The arginine at codon 2467 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
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 | Sep 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at