rs11571510
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The ENST00000330513.10(TGIF1):c.-202del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,590,158 control chromosomes in the GnomAD database, including 123,175 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.36 ( 10520 hom., cov: 30)
Exomes 𝑓: 0.39 ( 112655 hom. )
Consequence
TGIF1
ENST00000330513.10 5_prime_UTR
ENST00000330513.10 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.95
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 Benign. Variant got -16 ACMG points.
BP6
?
Variant 18-3452224-CT-C is Benign according to our data. Variant chr18-3452224-CT-C is described in ClinVar as [Benign]. Clinvar id is 403532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3452224-CT-C is described in Lovd as [Benign]. Variant chr18-3452224-CT-C is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGIF1 | NM_003244.4 | c.16+1720del | intron_variant | ENST00000343820.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGIF1 | ENST00000343820.10 | c.16+1720del | intron_variant | 1 | NM_003244.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.364 AC: 55004AN: 151196Hom.: 10512 Cov.: 30
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GnomAD3 exomes AF: 0.318 AC: 73899AN: 232656Hom.: 12428 AF XY: 0.325 AC XY: 41340AN XY: 127308
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GnomAD4 exome AF: 0.390 AC: 561642AN: 1438844Hom.: 112655 Cov.: 0 AF XY: 0.388 AC XY: 277717AN XY: 715418
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GnomAD4 genome ? AF: 0.364 AC: 55034AN: 151314Hom.: 10520 Cov.: 30 AF XY: 0.358 AC XY: 26444AN XY: 73900
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 11, 2019 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 542/2178=24.88% - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Computational scores
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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