11-126293796-A-G

Variant names:

• chr11-126293796-A-G
• rs611953
• NM_001318777.2:c.*109A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0640

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]

ENSG00000254905 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
TIRAP	NM_001318777.2	c.*109A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000392679.6	NP_001305706.1
TIRAP	NM_001039661.2	c.*109A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001034750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000392679.6	c.*109A>G		3_prime_UTR_variant	Exon 5 of 5	2	NM_001318777.2	ENSP00000376446.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110850 AN: 151992 Hom.: 41498 Cov.: 32

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

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.: 14 AF XY: 0.784 AC XY: 442300 AN XY: 563996

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.: 32 AF XY: 0.739 AC XY: 54978 AN XY: 74350

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

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 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

Other links and lift over

dbSNP: rs611953; hg19: chr11-126163691;