11-126295862-T-C

Position:

• chr11-126295862-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000479770.2(TIRAP):​c.*952+1223T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,084 control chromosomes in the GnomAD database, including 4,351 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4351 hom., cov: 31)
• Consequence: TIRAP ENST00000479770.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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-AS1 (HGNC:56069): (TIRAP antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIRAP-AS1	XR_948146.4	n.2823+1106A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIRAP-AS1	ENST00000524964.2	n.117-1260A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31630 AN: 151964 Hom.: 4350 Cov.: 31

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31633 AN: 152084 Hom.: 4351 Cov.: 31 AF XY: 0.220 AC XY: 16319 AN XY: 74336

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.216

Alfa AF: 0.156 Hom.: 464

Bravo AF: 0.213

Asia WGS AF: 0.452 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1786704; hg19: chr11-126165757;