rs1037180469
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_001110556.2(FLNA):c.2826+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,097,061 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001110556.2 splice_donor_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.2826+4G>A | splice_donor_region_variant, intron_variant | ENST00000369850.10 | |||
FLNA | NM_001456.4 | c.2826+4G>A | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.2826+4G>A | splice_donor_region_variant, intron_variant | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 110539Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 32761 FAILED QC
GnomAD3 exomes AF: 0.00000553 AC: 1AN: 180868Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67262
GnomAD4 exome AF: 0.0000264 AC: 29AN: 1097061Hom.: 0 Cov.: 32 AF XY: 0.0000221 AC XY: 8AN XY: 362665
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 110539Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 32761
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2021 | The c.2826+4G>A intronic variant results from a G to A substitution 4 nucleotides after coding exon 18 in the FLNA gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | This sequence change falls in intron 19 of the FLNA gene. It does not directly change the encoded amino acid sequence of the FLNA protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 464981). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at