Variant 11-126292967-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001318777.2(TIRAP):c.558C>T(p.Ala186Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,613,986 control chromosomes in the GnomAD database, including 41,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 2928 hom., cov: 33)

Exomes 𝑓: 0.22 ( 38757 hom. )

Consequence

TIRAP
NM_001318777.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.357

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:

ENSG00000254905 (HGNC:):

ENSG00000254905 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 11-126292967-C-T is Benign according to our data. Variant chr11-126292967-C-T is described in ClinVar as [Benign]. Clinvar id is 2688488.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.357 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIRAP	NM_001318777.2 link	c.558C>T	p.Ala186Ala	synonymous_variant	Exon 4 of 5	ENST00000392679.6	NP_001305706.1	P58753-1A0A024R3M4
TIRAP	NM_001318776.2 link	c.558C>T	p.Ala186Ala	synonymous_variant	Exon 4 of 4		NP_001305705.1	P58753-2
TIRAP	NM_148910.3 link	c.558C>T	p.Ala186Ala	synonymous_variant	Exon 5 of 5		NP_683708.1	P58753-2
TIRAP	NM_001039661.2 link	c.558C>T	p.Ala186Ala	synonymous_variant	Exon 5 of 6		NP_001034750.1	P58753-1A0A024R3M4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000392679.6 link	c.558C>T	p.Ala186Ala	synonymous_variant	Exon 4 of 5	2	NM_001318777.2	ENSP00000376446.1		P58753-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28420

AN:

152108

Hom.:

2925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.0333

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.178

AC:

44631

AN:

250232

Hom.:

4659

AF XY:

0.183

AC XY:

24738

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0952

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0289

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.223

AC:

325954

AN:

1461760

Hom.:

38757

Cov.:

AF XY:

0.222

AC XY:

161407

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.181

Gnomad4 EAS exome

AF:

0.0353

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.187

AC:

28436

AN:

152226

Hom.:

2928

Cov.:

AF XY:

0.180

AC XY:

13397

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.0333

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.222

Hom.:

5079

Bravo

AF:

0.180

Asia WGS

AF:

0.0940

AC:

330

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.72

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