Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_018723.4(RBFOX1):c.1057G>A(p.Gly353Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,612,934 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G353G) has been classified as Likely benign.
RBFOX1 (HGNC:18222): (RNA binding fox-1 homolog 1) The Fox-1 family of RNA-binding proteins is evolutionarily conserved, and regulates tissue-specific alternative splicing in metazoa. Fox-1 recognizes a (U)GCAUG stretch in regulated exons or in flanking introns. The protein binds to the C-terminus of ataxin-2 and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the product of the SCA2 gene which causes familial neurodegenerative diseases. Fox-1 and ataxin-2 are both localized in the trans-Golgi network. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
RBFOX1 Gene-Disease associations (from GenCC):
epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P
autism susceptibility 1
Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine
Our verdict: Benign. The variant received -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.010302544).
BP6
Variant 16-7709117-G-A is Benign according to our data. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709117-G-A is described in CliVar as Likely_benign. Clinvar id is 433121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Self-limited epilepsy with centrotemporal spikesPathogenic:1
Jan 01, 2017
Bioinformatics Core, Luxembourg Center for Systems Biomedicine
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:case-control
CAADphred>15 -
RBFOX1-related disorderBenign:1
Jul 28, 2022
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
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). -