11-126292712-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_001318777.2(TIRAP):c.303G>A(p.Gln101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,300 control chromosomes in the GnomAD database, including 16,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.10 ( 1091 hom., cov: 32)
Exomes 𝑓: 0.14 ( 15303 hom. )
Consequence
TIRAP
NM_001318777.2 synonymous
NM_001318777.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.04
Genes affected
TIRAP (HGNC:17192): (TIR domain containing adaptor protein) The innate immune system recognizes microbial pathogens through Toll-like receptors (TLRs), which identify pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns and all TLRs have a Toll-interleukin 1 receptor (TIR) domain, which is responsible for signal transduction. The protein encoded by this gene is a TIR adaptor protein involved in the TLR4 signaling pathway of the immune system. It activates NF-kappa-B, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]
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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=-0.61).
BP6
Variant 11-126292712-G-A is Benign according to our data. Variant chr11-126292712-G-A is described in ClinVar as [Benign]. Clinvar id is 2688487.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=3.04 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TIRAP | NM_001318777.2 | c.303G>A | p.Gln101= | synonymous_variant | 4/5 | ENST00000392679.6 | NP_001305706.1 | |
TIRAP | NM_001318776.2 | c.303G>A | p.Gln101= | synonymous_variant | 4/4 | NP_001305705.1 | ||
TIRAP | NM_148910.3 | c.303G>A | p.Gln101= | synonymous_variant | 5/5 | NP_683708.1 | ||
TIRAP | NM_001039661.2 | c.303G>A | p.Gln101= | synonymous_variant | 5/6 | NP_001034750.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TIRAP | ENST00000392679.6 | c.303G>A | p.Gln101= | synonymous_variant | 4/5 | 2 | NM_001318777.2 | ENSP00000376446 | P1 |
Frequencies
GnomAD3 genomes AF: 0.105 AC: 15979AN: 152152Hom.: 1091 Cov.: 32
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GnomAD3 exomes AF: 0.116 AC: 28825AN: 248808Hom.: 1934 AF XY: 0.122 AC XY: 16420AN XY: 134646
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GnomAD4 exome AF: 0.140 AC: 204168AN: 1461030Hom.: 15303 Cov.: 34 AF XY: 0.140 AC XY: 102022AN XY: 726746
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GnomAD4 genome AF: 0.105 AC: 15973AN: 152270Hom.: 1091 Cov.: 32 AF XY: 0.106 AC XY: 7869AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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