chr11-126292948-C-T

Position:

chr11-126292948-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001318777.2(TIRAP):c.539C>T(p.Ser180Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,956 control chromosomes in the GnomAD database, including 18,397 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1228 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17169 hom. )

Consequence

TIRAP
NM_001318777.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.751

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016107559).

BP6

Variant 11-126292948-C-T is Benign according to our data. Variant chr11-126292948-C-T is described in ClinVar as [Benign]. Clinvar id is 4467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TIRAP	NM_001318777.2 linkuse as main transcript	c.539C>T	p.Ser180Leu	missense_variant	4/5	ENST00000392679.6	NP_001305706.1
TIRAP	NM_001318776.2 linkuse as main transcript	c.539C>T	p.Ser180Leu	missense_variant	4/4		NP_001305705.1
TIRAP	NM_148910.3 linkuse as main transcript	c.539C>T	p.Ser180Leu	missense_variant	5/5		NP_683708.1
TIRAP	NM_001039661.2 linkuse as main transcript	c.539C>T	p.Ser180Leu	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.539C>T	p.Ser180Leu	missense_variant	4/5	2	NM_001318777.2	ENSP00000376446	P1	P58753-1
	ENST00000533378.1 linkuse as main transcript	n.466G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16910

AN:

152142

Hom.:

1228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.0127

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.124

AC:

30945

AN:

250244

Hom.:

2234

AF XY:

0.130

AC XY:

17565

AN XY:

135440

show subpopulations

Gnomad AFR exome

AF:

0.0262

Gnomad AMR exome

AF:

0.0740

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.0121

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.148

AC:

216650

AN:

1461696

Hom.:

17169

Cov.:

AF XY:

0.149

AC XY:

108156

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0237

Gnomad4 AMR exome

AF:

0.0773

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.0200

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.111

AC:

16904

AN:

152260

Hom.:

1228

Cov.:

AF XY:

0.111

AC XY:

8291

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.0129

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.146

Hom.:

3606

Bravo

AF:

0.103

TwinsUK

AF:

0.155

AC:

576

ALSPAC

AF:

0.164

AC:

633

ESP6500AA

AF:

0.0304

AC:

134

ESP6500EA

AF:

0.158

AC:

1362

ExAC

AF:

0.124

AC:

15074

Asia WGS

AF:

0.0790

AC:

276

AN:

3478

EpiCase

AF:

0.159

EpiControl

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	This variant is associated with the following publications: (PMID: 26771213, 20525286, 22683004, 18417424, 19456234, 18305471, 22058078, 19509334, 21705416, 17322885, 25003251, 26885859, 27166096, 24067789, 23047423, 26614847, 20797905) -

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

Bacteremia, susceptibility

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jun 20, 2020

- -

Invasive pneumococcal disease, protection against

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Mar 01, 2008

- -

Mycobacterium tuberculosis, protection against

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Mar 01, 2008

- -

Malaria, resistance to

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jun 20, 2020

- -

Mycobacterium tuberculosis, susceptibility to;C1970028:Malaria, susceptibility to;C3280645:Bacteremia, susceptibility to, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 27, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.031

T;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.64

.;T;.

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.71

N;N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.092

Sift

Benign

0.53

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.46

P;.;P

Vest4

0.057

MPC

0.15

ClinPred

0.024

GERP RS

4.7

Varity_R

0.18

gMVP

0.47

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over