chr18-3449607-T-TGCGCC
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The XR_007066269.1(LOC124904237):n.125+924_125+925insGGCGC variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 945,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000035 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
LOC124904237
XR_007066269.1 intron, non_coding_transcript
XR_007066269.1 intron, non_coding_transcript
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.56
Genes affected
TGIF1 (HGNC:11776): (TGFB induced factor homeobox 1) The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 18-3449607-T-TGCGCC is Benign according to our data. Variant chr18-3449607-T-TGCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 3032359.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOC124904237 | XR_007066269.1 | n.125+924_125+925insGGCGC | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGIF1 | ENST00000549253.5 | c.-83_-79dup | 5_prime_UTR_variant | 1/3 | 3 | ||||
TGIF1 | ENST00000401449.5 | c.-44-6736_-44-6732dup | intron_variant | 2 | |||||
TGIF1 | ENST00000548489.6 | c.-44-6736_-44-6732dup | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000355 AC: 4AN: 112686Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.0000228 AC: 19AN: 833148Hom.: 0 Cov.: 36 AF XY: 0.0000234 AC XY: 9AN XY: 384746
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GnomAD4 genome AF: 0.0000355 AC: 4AN: 112686Hom.: 0 Cov.: 31 AF XY: 0.0000586 AC XY: 3AN XY: 51234
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
TGIF1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 15, 2020 | 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). - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at