rs370042010
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001458.5(FLNC):c.3872G>A(p.Arg1291His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000991 in 1,613,784 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3872G>A | p.Arg1291His | missense_variant | Exon 22 of 48 | 1 | NM_001458.5 | ENSP00000327145.8 | ||
FLNC | ENST00000346177.6 | c.3872G>A | p.Arg1291His | missense_variant | Exon 22 of 47 | 1 | ENSP00000344002.6 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000805 AC: 20AN: 248382Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 135052
GnomAD4 exome AF: 0.000102 AC: 149AN: 1461634Hom.: 1 Cov.: 34 AF XY: 0.0000990 AC XY: 72AN XY: 727136
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
- -
FLNC: BP4, BS2 -
- -
Cardiovascular phenotype Uncertain:1
The p.R1291H variant (also known as c.3872G>A), located in coding exon 22 of the FLNC gene, results from a G to A substitution at nucleotide position 3872. The arginine at codon 1291 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant 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
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at