11-126295862-T-C

Variant names:

• chr11-126295862-T-C
• rs1786704
• ENST00000479770.2:n.*952+1223T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000700493.1(TIRAP):​n.4486T>C variant causes a non coding transcript exon 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 ENST00000700493.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000700493.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP-AS1	NR_187383.1		n.116-1260A>G		intron	N/A
	TIRAP-AS1	NR_187384.1		n.136-1206A>G		intron	N/A
	TIRAP-AS1	NR_187385.1		n.116-1268A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	ENST00000479770.2	TSL:1	n.*952+1223T>C		intron	N/A	ENSP00000436967.1
	TIRAP	ENST00000700493.1		n.4486T>C		non_coding_transcript_exon	Exon 4 of 4
	TIRAP	ENST00000700496.1		n.2916T>C		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AF: 0.0876 AC: 3638 AN: 41514

American (AMR) AF: 0.326 AC: 4976 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3311 AN: 5166

South Asian (SAS) AF: 0.342 AC: 1649 AN: 4818

European-Finnish (FIN) AF: 0.247 AC: 2608 AN: 10564

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13966 AN: 67984

Other (OTH) AF: 0.216 AC: 455 AN: 2110

Alfa AF: 0.155 Hom.: 470

Bravo AF: 0.213

Asia WGS AF: 0.452 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.93
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs1786704; hg19: chr11-126165757;