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11-126292802-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001318777.2(TIRAP):c.393C>T(p.Ser131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000778 in 1,612,934 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

TIRAP
NM_001318777.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.82
Variant links:
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 -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-126292802-C-T is Benign according to our data. Variant chr11-126292802-C-T is described in ClinVar as [Benign]. Clinvar id is 3034958.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.82 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TIRAPNM_001318777.2 linkuse as main transcriptc.393C>T p.Ser131= synonymous_variant 4/5 ENST00000392679.6
TIRAPNM_001318776.2 linkuse as main transcriptc.393C>T p.Ser131= synonymous_variant 4/4
TIRAPNM_148910.3 linkuse as main transcriptc.393C>T p.Ser131= synonymous_variant 5/5
TIRAPNM_001039661.2 linkuse as main transcriptc.393C>T p.Ser131= synonymous_variant 5/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TIRAPENST00000392679.6 linkuse as main transcriptc.393C>T p.Ser131= synonymous_variant 4/52 NM_001318777.2 P1P58753-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00422
AC:
643
AN:
152206
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0147
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000963
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00110
AC:
273
AN:
248160
Hom.:
2
AF XY:
0.000855
AC XY:
115
AN XY:
134470
show subpopulations
Gnomad AFR exome
AF:
0.0155
Gnomad AMR exome
AF:
0.000262
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000491
Gnomad SAS exome
AF:
0.0000986
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.000417
AC:
609
AN:
1460610
Hom.:
3
Cov.:
34
AF XY:
0.000366
AC XY:
266
AN XY:
726564
show subpopulations
Gnomad4 AFR exome
AF:
0.0149
Gnomad4 AMR exome
AF:
0.000381
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000403
Gnomad4 SAS exome
AF:
0.0000813
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00101
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00424
AC:
646
AN:
152324
Hom.:
6
Cov.:
32
AF XY:
0.00430
AC XY:
320
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0147
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000965
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00230
Hom.:
2
Bravo
AF:
0.00479
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TIRAP-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJan 23, 2024This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
0.13
Dann
Benign
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142475083; hg19: chr11-126162697; API