14-28767300-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_005249.5(FOXG1):c.21G>A(p.Arg7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000069 ( 0 hom., cov: 30)
Exomes 𝑓: 7.8e-7 ( 0 hom. )
Consequence
FOXG1
NM_005249.5 synonymous
NM_005249.5 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 2.58
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP7
Synonymous conserved (PhyloP=2.58 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.21G>A | p.Arg7= | synonymous_variant | 1/1 | ENST00000313071.7 | NP_005240.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.21G>A | p.Arg7= | synonymous_variant | 1/1 | NM_005249.5 | ENSP00000339004 | P1 | ||
FOXG1 | ENST00000706482.1 | c.21G>A | p.Arg7= | synonymous_variant | 2/2 | ENSP00000516406 | P1 | |||
LINC01551 | ENST00000675861.1 | n.374+1287G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000687 AC: 1AN: 145536Hom.: 0 Cov.: 30
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GnomAD4 exome AF: 7.76e-7 AC: 1AN: 1288648Hom.: 0 Cov.: 32 AF XY: 0.00000156 AC XY: 1AN XY: 640056
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GnomAD4 genome AF: 0.00000687 AC: 1AN: 145536Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 70762
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rett syndrome, congenital variant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 10, 2024 | This sequence change affects codon 7 of the FOXG1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FOXG1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FOXG1-related conditions. 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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