chr11-126292573-G-A

Position:

chr11-126292573-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001318777.2(TIRAP):c.164G>A(p.Ser55Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,613,986 control chromosomes in the GnomAD database, including 3,252 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.062 ( 417 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2835 hom. )

Consequence

TIRAP
NM_001318777.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.473

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012226701).

BP6

Variant 11-126292573-G-A is Benign according to our data. Variant chr11-126292573-G-A is described in ClinVar as [Benign]. Clinvar id is 2688471.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 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.164G>A	p.Ser55Asn	missense_variant	4/5	ENST00000392679.6	NP_001305706.1
TIRAP	NM_001318776.2 linkuse as main transcript	c.164G>A	p.Ser55Asn	missense_variant	4/4		NP_001305705.1
TIRAP	NM_148910.3 linkuse as main transcript	c.164G>A	p.Ser55Asn	missense_variant	5/5		NP_683708.1
TIRAP	NM_001039661.2 linkuse as main transcript	c.164G>A	p.Ser55Asn	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.164G>A	p.Ser55Asn	missense_variant	4/5	2	NM_001318777.2	ENSP00000376446	P1	P58753-1

Frequencies

GnomAD3 genomes

AF:

0.0620

AC:

9420

AN:

152056

Hom.:

416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.0802

Gnomad FIN

AF:

0.0665

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0413

Gnomad OTH

AF:

0.0647

GnomAD3 exomes

AF:

0.0776

AC:

19476

AN:

251124

Hom.:

1221

AF XY:

0.0726

AC XY:

9850

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.0368

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.0688

Gnomad FIN exome

AF:

0.0687

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0496

AC:

72462

AN:

1461812

Hom.:

2835

Cov.:

AF XY:

0.0498

AC XY:

36231

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0562

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.0376

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.0704

Gnomad4 FIN exome

AF:

0.0679

Gnomad4 NFE exome

AF:

0.0375

Gnomad4 OTH exome

AF:

0.0534

GnomAD4 genome

AF:

0.0620

AC:

9433

AN:

152174

Hom.:

417

Cov.:

AF XY:

0.0657

AC XY:

4890

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0547

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.0790

Gnomad4 FIN

AF:

0.0665

Gnomad4 NFE

AF:

0.0413

Gnomad4 OTH

AF:

0.0654

Alfa

AF:

0.0465

Hom.:

525

Bravo

AF:

0.0651

TwinsUK

AF:

0.0372

AC:

138

ALSPAC

AF:

0.0420

AC:

162

ESP6500AA

AF:

0.0618

AC:

272

ESP6500EA

AF:

0.0370

AC:

318

ExAC

AF:

0.0733

AC:

8899

Asia WGS

AF:

0.143

AC:

497

AN:

3478

EpiCase

AF:

0.0395

EpiControl

AF:

0.0397

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

TIRAP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2019

This 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

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.5

DANN

Benign

0.57

DEOGEN2

Benign

0.15

T;.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.28

.;T;.

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

L;L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.86

N;N;N

REVEL

Benign

0.086

Sift

Benign

0.88

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0030

B;.;B

Vest4

0.025

MPC

0.027

ClinPred

0.00084

GERP RS

-2.1

Varity_R

0.044

gMVP

0.33

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