rs527248119
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001458.5(FLNC):c.6988G>A(p.Gly2330Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,612,302 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2330D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.6988G>A | p.Gly2330Ser | missense_variant | 41/48 | ENST00000325888.13 | |
FLNC-AS1 | NR_149055.1 | n.103-1276C>T | intron_variant, non_coding_transcript_variant | ||||
FLNC | NM_001127487.2 | c.6889G>A | p.Gly2297Ser | missense_variant | 40/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.6988G>A | p.Gly2330Ser | missense_variant | 41/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.6889G>A | p.Gly2297Ser | missense_variant | 40/47 | 1 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.103-1276C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152220Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000663 AC: 163AN: 246020Hom.: 2 AF XY: 0.000844 AC XY: 113AN XY: 133910
GnomAD4 exome AF: 0.000425 AC: 620AN: 1459966Hom.: 7 Cov.: 33 AF XY: 0.000525 AC XY: 381AN XY: 726150
GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152336Hom.: 1 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74488
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 14, 2021 | This variant is associated with the following publications: (PMID: 28356264) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | FLNC: BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 15, 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at