rs757233206
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001458.5(FLNC):c.5202G>A(p.Ala1734=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,587,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001458.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.5202G>A | p.Ala1734= | splice_region_variant, synonymous_variant | 31/48 | ENST00000325888.13 | NP_001449.3 | |
FLNC | NM_001127487.2 | c.5199+400G>A | intron_variant | NP_001120959.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.5202G>A | p.Ala1734= | splice_region_variant, synonymous_variant | 31/48 | 1 | NM_001458.5 | ENSP00000327145 | P3 | |
FLNC | ENST00000346177.6 | c.5199+400G>A | intron_variant | 1 | ENSP00000344002 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000432 AC: 9AN: 208552Hom.: 0 AF XY: 0.0000262 AC XY: 3AN XY: 114326
GnomAD4 exome AF: 0.0000174 AC: 25AN: 1435276Hom.: 0 Cov.: 32 AF XY: 0.0000168 AC XY: 12AN XY: 712876
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | FLNC: BP4, BP7 - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 14, 2020 | 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
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 18, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at