11-126293169-A-G

Variant names:

• chr11-126293169-A-G
• rs8177375
• ENST00000392678.7:c.*52A>G

Variant summary

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

The ENST00000392678.7(TIRAP):​c.*52A>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 0.123 in 1,566,470 control chromosomes in the GnomAD database, including 12,227 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 0.13 (1229 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10998 hom.)
• Consequence: TIRAP ENST00000392678.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 28 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]

ENSG00000254905 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392678.7. 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	NM_001318777.2	MANE Select	c.646+114A>G		intron	N/A	NP_001305706.1
	TIRAP	NM_001318776.2		c.*52A>G		3_prime_UTR	Exon 4 of 4	NP_001305705.1
	TIRAP	NM_148910.3		c.*52A>G		3_prime_UTR	Exon 5 of 5	NP_683708.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	ENST00000392678.7	TSL:1	c.*52A>G		3_prime_UTR	Exon 5 of 5	ENSP00000376445.3
	TIRAP	ENST00000392679.6	TSL:2 MANE Select	c.646+114A>G		intron	N/A	ENSP00000376446.1
	TIRAP	ENST00000392680.6	TSL:1	c.646+114A>G		intron	N/A	ENSP00000376447.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19009 AN: 152034 Hom.: 1227 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0892

GnomAD2 exomes AF: 0.121 AC: 24975 AN: 207238 AF XY: 0.122

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.0665

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.130

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.123 AC: 173874 AN: 1414318 Hom.: 10998 Cov.: 30 AF XY: 0.124 AC XY: 86662 AN XY: 700534

African (AFR) AF: 0.137 AC: 4458 AN: 32474

American (AMR) AF: 0.0684 AC: 2788 AN: 40762

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3412 AN: 24304

East Asian (EAS) AF: 0.135 AC: 5308 AN: 39226

South Asian (SAS) AF: 0.144 AC: 11824 AN: 81998

European-Finnish (FIN) AF: 0.143 AC: 5772 AN: 40468

Middle Eastern (MID) AF: 0.139 AC: 779 AN: 5622

European-Non Finnish (NFE) AF: 0.121 AC: 132312 AN: 1090770

Other (OTH) AF: 0.123 AC: 7221 AN: 58694

GnomAD4 genome AF: 0.125 AC: 19020 AN: 152152 Hom.: 1229 Cov.: 33 AF XY: 0.126 AC XY: 9389 AN XY: 74368

African (AFR) AF: 0.142 AC: 5908 AN: 41488

American (AMR) AF: 0.0814 AC: 1245 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3472

East Asian (EAS) AF: 0.129 AC: 670 AN: 5188

South Asian (SAS) AF: 0.140 AC: 675 AN: 4822

European-Finnish (FIN) AF: 0.151 AC: 1598 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8126 AN: 67984

Other (OTH) AF: 0.0949 AC: 200 AN: 2108

Alfa AF: 0.116 Hom.: 1894

Bravo AF: 0.119

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.65
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs8177375; hg19: chr11-126163064; COSMIC: COSV67023985; COSMIC: COSV67023985;