12-57466263-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_005269.3(GLI1):c.786C>T(p.His262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,613,368 control chromosomes in the GnomAD database, including 1,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.056 ( 491 hom., cov: 32)
Exomes 𝑓: 0.023 ( 817 hom. )
Consequence
GLI1
NM_005269.3 synonymous
NM_005269.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.84
Genes affected
GLI1 (HGNC:4317): (GLI family zinc finger 1) This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 12-57466263-C-T is Benign according to our data. Variant chr12-57466263-C-T is described in ClinVar as [Benign]. Clinvar id is 3056398.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.84 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLI1 | NM_005269.3 | c.786C>T | p.His262= | synonymous_variant | 8/12 | ENST00000228682.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLI1 | ENST00000228682.7 | c.786C>T | p.His262= | synonymous_variant | 8/12 | 1 | NM_005269.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0563 AC: 8565AN: 152052Hom.: 487 Cov.: 32
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GnomAD3 exomes AF: 0.0322 AC: 8062AN: 250590Hom.: 317 AF XY: 0.0316 AC XY: 4287AN XY: 135470
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GnomAD4 exome AF: 0.0227 AC: 33231AN: 1461198Hom.: 817 Cov.: 32 AF XY: 0.0234 AC XY: 17037AN XY: 726900
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GnomAD4 genome ? AF: 0.0564 AC: 8582AN: 152170Hom.: 491 Cov.: 32 AF XY: 0.0566 AC XY: 4207AN XY: 74376
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GLI1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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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