rs201672146
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001458.5(FLNC):c.7091G>A(p.Arg2364His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,614,062 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.7091G>A | p.Arg2364His | missense_variant | Exon 42 of 48 | ENST00000325888.13 | NP_001449.3 | |
FLNC | NM_001127487.2 | c.6992G>A | p.Arg2331His | missense_variant | Exon 41 of 47 | NP_001120959.1 | ||
FLNC-AS1 | NR_149055.1 | n.103-1471C>T | intron_variant | Intron 1 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.7091G>A | p.Arg2364His | missense_variant | Exon 42 of 48 | 1 | NM_001458.5 | ENSP00000327145.8 | ||
FLNC | ENST00000346177.6 | c.6992G>A | p.Arg2331His | missense_variant | Exon 41 of 47 | 1 | ENSP00000344002.6 | |||
FLNC-AS1 | ENST00000469965.1 | n.103-1471C>T | intron_variant | Intron 1 of 3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00165 AC: 251AN: 152160Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00178 AC: 443AN: 249400Hom.: 1 AF XY: 0.00169 AC XY: 229AN XY: 135314
GnomAD4 exome AF: 0.00285 AC: 4167AN: 1461784Hom.: 8 Cov.: 33 AF XY: 0.00281 AC XY: 2047AN XY: 727202
GnomAD4 genome AF: 0.00165 AC: 251AN: 152278Hom.: 1 Cov.: 33 AF XY: 0.00146 AC XY: 109AN XY: 74448
ClinVar
Submissions by phenotype
not specified Benign:4
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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. -
Cardiomyopathy Benign:1
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not provided Benign:1
FLNC: BS1 -
FLNC-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Cardiovascular phenotype Benign:1
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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at