Variant 11-126293717-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001318777.2(TIRAP):c.*30T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,612,412 control chromosomes in the GnomAD database, including 41,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2702 hom., cov: 32)

Exomes 𝑓: 0.22 ( 38537 hom. )

Consequence

TIRAP
NM_001318777.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.909

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 11-126293717-T-G is Benign according to our data. Variant chr11-126293717-T-G is described in ClinVar as [Benign]. Clinvar id is 2688489.Status of the report is criteria_provided_single_submitter, 1 stars.

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/exons	MANE	Protein	UniProt
TIRAP	NM_001318777.2 linkuse as main transcript	c.*30T>G		3_prime_UTR_variant	5/5	ENST00000392679.6	NP_001305706.1
TIRAP	NM_001039661.2 linkuse as main transcript	c.*30T>G		3_prime_UTR_variant	6/6		NP_001034750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000392679.6 linkuse as main transcript	c.*30T>G		3_prime_UTR_variant	5/5	2	NM_001318777.2	ENSP00000376446	P1	P58753-1
	ENST00000533378.1 linkuse as main transcript	n.127+411A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26524

AN:

151966

Hom.:

2700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0877

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.0332

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.175

AC:

44010

AN:

251374

Hom.:

4618

AF XY:

0.180

AC XY:

24494

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0832

Gnomad AMR exome

AF:

0.0927

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0290

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.222

AC:

323489

AN:

1460328

Hom.:

38537

Cov.:

AF XY:

0.221

AC XY:

160384

AN XY:

726550

show subpopulations

Gnomad4 AFR exome

AF:

0.0841

Gnomad4 AMR exome

AF:

0.0975

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:

0.246

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.174

AC:

26534

AN:

152084

Hom.:

2702

Cov.:

AF XY:

0.168

AC XY:

12497

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0877

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.0332

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.221

Hom.:

4288

Bravo

AF:

0.165

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

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 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

-0.76

CADD

Benign

7.2

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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