rs587783634
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_005249.5(FOXG1):c.209_235del(p.Gln70_Pro78del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,091,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★★). Synonymous variant affecting the same amino acid position (i.e. P65P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
FOXG1
NM_005249.5 inframe_deletion
NM_005249.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.38
Genes affected
FOXG1 (HGNC:3811): (forkhead box G1) This locus encodes a member of the fork-head transcription factor family. The encoded protein, which functions as a transcriptional repressor, is highly expressed in neural tissues during brain development. Mutations at this locus have been associated with Rett syndrome and a diverse spectrum of neurodevelopmental disorders defined as part of the FOXG1 syndrome. This gene is disregulated in many types of cancer and is the target of multiple microRNAs that regulate the proliferation of tumor cells. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
?
Variant 14-28767471-ACCGCCGCCGCCGCCGCAGCAGCAGCAG-A is Benign according to our data. Variant chr14-28767471-ACCGCCGCCGCCGCCGCAGCAGCAGCAG-A is described in ClinVar as [Benign]. Clinvar id is 158592.Status of the report is reviewed_by_expert_panel, 3 stars.
BS2
?
High AC in GnomAd at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.209_235del | p.Gln70_Pro78del | inframe_deletion | 1/1 | ENST00000313071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.209_235del | p.Gln70_Pro78del | inframe_deletion | 1/1 | NM_005249.5 | P1 | ||
FOXG1 | ENST00000706482.1 | c.209_235del | p.Gln70_Pro78del | inframe_deletion | 2/2 | P1 | |||
LINC01551 | ENST00000675861.1 | n.374+1475_374+1501del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000163 AC: 21AN: 128906Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000257 AC: 19AN: 73900Hom.: 0 AF XY: 0.000258 AC XY: 11AN XY: 42564
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GnomAD4 exome AF: 0.000132 AC: 127AN: 962086Hom.: 0 AF XY: 0.000135 AC XY: 63AN XY: 467330
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ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:5
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Rett syndrome, congenital variant Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 06, 2014 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 21, 2017 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 17, 2017 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 05, 2020 | - - |
FOXG1 disorder Benign:1
Benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Apr 14, 2023 | The allele frequency of the c.209_235del variant in FOXG1 is 0.17% in Ashkenazi Jewish sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions BA1). The p.Gln70_Pro78del variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Gln70_Pro78del variant is an in-frame deletion present in a repetitive region of FOXG1 (BP3). In summary, the p.Gln70_Pro78del variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP3). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at