Variant chr11-126290792-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.-92-11A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,503,694 control chromosomes in the GnomAD database, including 18,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1472 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16623 hom. )

Consequence

TIRAP
NM_001318777.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002569

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.368

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 (BayesDel_noAF=-0.84).

BP6

Variant 11-126290792-A-G is Benign according to our data. Variant chr11-126290792-A-G is described in ClinVar as [Benign]. Clinvar id is 2688499.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TIRAP	NM_001318777.2 linkuse as main transcript	c.-92-11A>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000392679.6
TIRAP	NM_001039661.2 linkuse as main transcript	c.-92-11A>G	splice_polypyrimidine_tract_variant, intron_variant
TIRAP	NM_001318776.2 linkuse as main transcript	c.-92-11A>G	splice_polypyrimidine_tract_variant, intron_variant
TIRAP	NM_148910.3 linkuse as main transcript	c.-92-11A>G	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIRAP	ENST00000392679.6 linkuse as main transcript	c.-92-11A>G		splice_polypyrimidine_tract_variant, intron_variant		2	NM_001318777.2	P1	P58753-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20057

AN:

151938

Hom.:

1470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0945

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.153

AC:

206915

AN:

1351638

Hom.:

16623

Cov.:

AF XY:

0.153

AC XY:

101860

AN XY:

666580

show subpopulations

Gnomad4 AFR exome

AF:

0.0862

Gnomad4 AMR exome

AF:

0.0956

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.0210

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.132

AC:

20064

AN:

152056

Hom.:

1472

Cov.:

AF XY:

0.132

AC XY:

9834

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0946

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.131

Hom.:

750

Bravo

AF:

0.126

Asia WGS

AF:

0.0860

AC:

302

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 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.3

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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