14-28767417-GCACCACCACCACCAC-GCACCACCAC
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_005249.5(FOXG1):c.156_161delCCACCA(p.His53_His54del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 1,385,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000021 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
FOXG1
NM_005249.5 disruptive_inframe_deletion
NM_005249.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.89
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 14-28767417-GCACCAC-G is Benign according to our data. Variant chr14-28767417-GCACCAC-G is described in ClinVar as [Likely_benign]. Clinvar id is 569855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAdExome4 at 56 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.156_161delCCACCA | p.His53_His54del | disruptive_inframe_deletion | 1/1 | ENST00000313071.7 | NP_005240.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.156_161delCCACCA | p.His53_His54del | disruptive_inframe_deletion | 1/1 | 6 | NM_005249.5 | ENSP00000339004.3 | ||
FOXG1 | ENST00000706482.1 | c.156_161delCCACCA | p.His53_His54del | disruptive_inframe_deletion | 2/2 | ENSP00000516406.1 | ||||
LINC01551 | ENST00000675861.1 | n.374+1422_374+1427delCCACCA | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.0000210 AC: 3AN: 143126Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000500 AC: 7AN: 139964Hom.: 0 AF XY: 0.0000392 AC XY: 3AN XY: 76586
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GnomAD4 exome AF: 0.0000451 AC: 56AN: 1242118Hom.: 0 AF XY: 0.0000504 AC XY: 31AN XY: 615016
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GnomAD4 genome AF: 0.0000210 AC: 3AN: 143126Hom.: 0 Cov.: 30 AF XY: 0.0000288 AC XY: 2AN XY: 69430
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 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 | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | FOXG1: BP3 - |
Rett syndrome, congenital variant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 12, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at