rs751592993
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001458.5(FLNC):c.4880G>A(p.Arg1627His) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,518 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).
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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.4880G>A | p.Arg1627His | missense_variant | Exon 28 of 48 | 1 | NM_001458.5 | ENSP00000327145.8 | ||
FLNC | ENST00000346177.6 | c.4880G>A | p.Arg1627His | missense_variant | Exon 28 of 47 | 1 | ENSP00000344002.6 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152058Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000204 AC: 5AN: 245250Hom.: 0 AF XY: 0.0000225 AC XY: 3AN XY: 133378
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461342Hom.: 0 Cov.: 35 AF XY: 0.0000165 AC XY: 12AN XY: 726964
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74390
ClinVar
Submissions by phenotype
not provided Uncertain:3
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In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Cardiovascular phenotype Uncertain:1
The p.R1627H variant (also known as c.4880G>A), located in coding exon 28 of the FLNC gene, results from a G to A substitution at nucleotide position 4880. The arginine at codon 1627 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at