Variant chr11-126293796-A-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.*109A>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 0.775 in 1,253,056 control chromosomes in the GnomAD database, including 380,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.73 ( 41535 hom., cov: 32)

Exomes 𝑓: 0.78 ( 338873 hom. )

Consequence

TIRAP
NM_001318777.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0640

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=-0.86).

BP6

Variant 11-126293796-A-G is Benign according to our data. Variant chr11-126293796-A-G is described in ClinVar as [Benign]. Clinvar id is 2688423.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIRAP	NM_001318777.2 linkuse as main transcript	c.*109A>G		3_prime_UTR_variant	5/5	ENST00000392679.6
TIRAP	NM_001039661.2 linkuse as main transcript	c.*109A>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIRAP	ENST00000392679.6 linkuse as main transcript	c.*109A>G		3_prime_UTR_variant	5/5	2	NM_001318777.2	P1	P58753-1
	ENST00000533378.1 linkuse as main transcript	n.127+332T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.729

AC:

110850

AN:

151992

Hom.:

41498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.801

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.991

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.800

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.723

GnomAD3 exomes

AF:

0.796

AC:

189709

AN:

238380

Hom.:

76449

AF XY:

0.798

AC XY:

103041

AN XY:

129128

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.863

Gnomad ASJ exome

AF:

0.736

Gnomad EAS exome

AF:

0.989

Gnomad SAS exome

AF:

0.867

Gnomad FIN exome

AF:

0.784

Gnomad NFE exome

AF:

0.766

Gnomad OTH exome

AF:

0.776

GnomAD4 exome

AF:

0.781

AC:

859947

AN:

1100946

Hom.:

338873

Cov.:

AF XY:

0.784

AC XY:

442300

AN XY:

563996

show subpopulations

Gnomad4 AFR exome

AF:

0.548

Gnomad4 AMR exome

AF:

0.852

Gnomad4 ASJ exome

AF:

0.735

Gnomad4 EAS exome

AF:

0.994

Gnomad4 SAS exome

AF:

0.865

Gnomad4 FIN exome

AF:

0.780

Gnomad4 NFE exome

AF:

0.769

Gnomad4 OTH exome

AF:

0.772

GnomAD4 genome

AF:

0.729

AC:

110940

AN:

152110

Hom.:

41535

Cov.:

AF XY:

0.739

AC XY:

54978

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.563

Gnomad4 AMR

AF:

0.801

Gnomad4 ASJ

AF:

0.730

Gnomad4 EAS

AF:

0.991

Gnomad4 SAS

AF:

0.871

Gnomad4 FIN

AF:

0.800

Gnomad4 NFE

AF:

0.773

Gnomad4 OTH

AF:

0.726

Alfa

AF:

0.729

Hom.:

16178

Bravo

AF:

0.719

Asia WGS

AF:

0.912

AC:

3171

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 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.4

DANN

Benign

0.61

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