rs781929535
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001110556.2(FLNA):c.5763C>T(p.Ser1921=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,210,024 control chromosomes in the GnomAD database, including 1 homozygotes. There are 73 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000035 ( 0 hom., 1 hem., cov: 26)
Exomes 𝑓: 0.00012 ( 1 hom. 72 hem. )
Consequence
FLNA
NM_001110556.2 synonymous
NM_001110556.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.51
Genes affected
FLNA (HGNC:3754): (filamin A) The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant X-154353651-G-A is Benign according to our data. Variant chrX-154353651-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.51 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000119 (131/1096804) while in subpopulation SAS AF= 0.0022 (119/54101). AF 95% confidence interval is 0.00188. There are 1 homozygotes in gnomad4_exome. There are 72 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAdExome4 at 72 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.5763C>T | p.Ser1921= | synonymous_variant | 36/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.5739C>T | p.Ser1913= | synonymous_variant | 35/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.5763C>T | p.Ser1921= | synonymous_variant | 36/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000353 AC: 4AN: 113167Hom.: 0 Cov.: 26 AF XY: 0.0000283 AC XY: 1AN XY: 35305
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GnomAD3 exomes AF: 0.000248 AC: 45AN: 181207Hom.: 1 AF XY: 0.000419 AC XY: 28AN XY: 66897
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GnomAD4 exome AF: 0.000119 AC: 131AN: 1096804Hom.: 1 Cov.: 33 AF XY: 0.000199 AC XY: 72AN XY: 362458
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GnomAD4 genome ? AF: 0.0000353 AC: 4AN: 113220Hom.: 0 Cov.: 26 AF XY: 0.0000283 AC XY: 1AN XY: 35368
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 28, 2016 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2020 | This alteration is classified as 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. - |
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | FLNA: BP4, BP7, BS2 - |
FLNA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 06, 2022 | 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). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at