Variant 11-126292809-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001318777.2(TIRAP):c.400T>C(p.Cys134Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000156 in 1,612,934 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00083 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

TIRAP
NM_001318777.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.14

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]

TIRAP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08197835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TIRAP	NM_001318777.2 linkuse as main transcript	c.400T>C	p.Cys134Arg	missense_variant	4/5	ENST00000392679.6	NP_001305706.1
TIRAP	NM_001318776.2 linkuse as main transcript	c.400T>C	p.Cys134Arg	missense_variant	4/4		NP_001305705.1
TIRAP	NM_148910.3 linkuse as main transcript	c.400T>C	p.Cys134Arg	missense_variant	5/5		NP_683708.1
TIRAP	NM_001039661.2 linkuse as main transcript	c.400T>C	p.Cys134Arg	missense_variant	5/6		NP_001034750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000392679.6 linkuse as main transcript	c.400T>C	p.Cys134Arg	missense_variant	4/5	2	NM_001318777.2	ENSP00000376446	P1	P58753-1

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000217

AC:

AN:

248448

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134516

show subpopulations

Gnomad AFR exome

AF:

0.00294

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000856

AC:

125

AN:

1460652

Hom.:

Cov.:

AF XY:

0.0000716

AC XY:

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.00329

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152282

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00298

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000222

Hom.:

Bravo

AF:

0.00102

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.63

.;T;.

M_CAP

Benign

0.047

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.86

MVP

0.89

MPC

0.27

ClinPred

0.13

GERP RS

5.7

Varity_R

0.95

gMVP

0.87

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over