chr7-128856859-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001458.5(FLNC):c.7499G>A(p.Ser2500Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.7499G>A | p.Ser2500Asn | missense_variant | Exon 45 of 48 | ENST00000325888.13 | NP_001449.3 | |
FLNC | NM_001127487.2 | c.7400G>A | p.Ser2467Asn | missense_variant | Exon 44 of 47 | NP_001120959.1 | ||
FLNC-AS1 | NR_149055.1 | n.103-3462C>T | intron_variant | Intron 1 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.7499G>A | p.Ser2500Asn | missense_variant | Exon 45 of 48 | 1 | NM_001458.5 | ENSP00000327145.8 | ||
FLNC | ENST00000346177.6 | c.7400G>A | p.Ser2467Asn | missense_variant | Exon 44 of 47 | 1 | ENSP00000344002.6 | |||
FLNC-AS1 | ENST00000469965.1 | n.103-3462C>T | intron_variant | Intron 1 of 3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000521 AC: 13AN: 249456Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135354
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727236
GnomAD4 genome AF: 0.000203 AC: 31AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 574790; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function -
The FLNC c.7499G>A; p.Ser2500Asn variant (rs371244800), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 574790). This variant is found in the African population with an allele frequency of 0.09% (21/24,198 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.421). Due to limited information, the clinical significance of this variant is uncertain at this time. -
- -
Cardiovascular phenotype Uncertain:1
The p.S2500N variant (also known as c.7499G>A), located in coding exon 45 of the FLNC gene, results from a G to A substitution at nucleotide position 7499. The serine at codon 2500 is replaced by asparagine, 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. 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
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at