Variant 11-126292712-G-A 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.303G>A(p.Gln101Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,300 control chromosomes in the GnomAD database, including 16,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 1091 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15303 hom. )

Consequence

TIRAP
NM_001318777.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.04

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 11-126292712-G-A is Benign according to our data. Variant chr11-126292712-G-A is described in ClinVar as [Benign]. Clinvar id is 2688487.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIRAP	NM_001318777.2 link	c.303G>A	p.Gln101Gln	synonymous_variant	Exon 4 of 5	ENST00000392679.6	NP_001305706.1	P58753-1A0A024R3M4
TIRAP	NM_001318776.2 link	c.303G>A	p.Gln101Gln	synonymous_variant	Exon 4 of 4		NP_001305705.1	P58753-2
TIRAP	NM_148910.3 link	c.303G>A	p.Gln101Gln	synonymous_variant	Exon 5 of 5		NP_683708.1	P58753-2
TIRAP	NM_001039661.2 link	c.303G>A	p.Gln101Gln	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.303G>A	p.Gln101Gln	synonymous_variant	Exon 4 of 5	2	NM_001318777.2	ENSP00000376446.1		P58753-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15979

AN:

152152

Hom.:

1091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.0964

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.116

AC:

28825

AN:

248808

Hom.:

1934

AF XY:

0.122

AC XY:

16420

AN XY:

134646

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.0696

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.0121

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.140

AC:

204168

AN:

1461030

Hom.:

15303

Cov.:

AF XY:

0.140

AC XY:

102022

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.0727

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0200

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.105

AC:

15973

AN:

152270

Hom.:

1091

Cov.:

AF XY:

0.106

AC XY:

7869

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.0962

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0131

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.131

Hom.:

1884

Bravo

AF:

0.0972

Asia WGS

AF:

0.0780

AC:

273

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

-0.61

CADD

Benign

3.7

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