11-126287084-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001318777.2(TIRAP):​c.-216-3378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,098 control chromosomes in the GnomAD database, including 5,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5577 hom., cov: 32)

Consequence

TIRAP
NM_001318777.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.683
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TIRAPNM_001318777.2 linkuse as main transcriptc.-216-3378C>T intron_variant ENST00000392679.6 NP_001305706.1 P58753-1A0A024R3M4
TIRAPNM_001318776.2 linkuse as main transcriptc.-216-3378C>T intron_variant NP_001305705.1 P58753-2
TIRAPNM_148910.3 linkuse as main transcriptc.-385-2581C>T intron_variant NP_683708.1 P58753-2
TIRAPNM_001039661.2 linkuse as main transcriptc.-369-2581C>T intron_variant NP_001034750.1 P58753-1A0A024R3M4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TIRAPENST00000392679.6 linkuse as main transcriptc.-216-3378C>T intron_variant 2 NM_001318777.2 ENSP00000376446.1 P58753-1

Frequencies

GnomAD3 genomes
AF:
0.241
AC:
36587
AN:
151980
Hom.:
5577
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0929
Gnomad AMI
AF:
0.167
Gnomad AMR
AF:
0.341
Gnomad ASJ
AF:
0.267
Gnomad EAS
AF:
0.637
Gnomad SAS
AF:
0.368
Gnomad FIN
AF:
0.348
Gnomad MID
AF:
0.247
Gnomad NFE
AF:
0.252
Gnomad OTH
AF:
0.234
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.241
AC:
36587
AN:
152098
Hom.:
5577
Cov.:
32
AF XY:
0.253
AC XY:
18804
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0926
Gnomad4 AMR
AF:
0.342
Gnomad4 ASJ
AF:
0.267
Gnomad4 EAS
AF:
0.637
Gnomad4 SAS
AF:
0.369
Gnomad4 FIN
AF:
0.348
Gnomad4 NFE
AF:
0.252
Gnomad4 OTH
AF:
0.233
Alfa
AF:
0.172
Hom.:
524
Bravo
AF:
0.237
Asia WGS
AF:
0.457
AC:
1585
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.6
DANN
Benign
0.43

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: rs595022; hg19: chr11-126156979; API