chr11-126297289-G-A

Variant names:

• chr11-126297289-G-A
• rs8177387
• ENST00000479770.2:n.*953-969G>A

Variant summary

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

The ENST00000479770.2(TIRAP):​n.*953-969G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 152,086 control chromosomes in the GnomAD database, including 439 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 0.064 (439 hom., cov: 33)
• Consequence: TIRAP ENST00000479770.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIRAP-AS1	NR_187389.1	n.492C>T		non_coding_transcript_exon_variant	Exon 1 of 2
TIRAP-AS1	NR_187383.1	n.116-2687C>T		intron_variant	Intron 1 of 1
TIRAP-AS1	NR_187384.1	n.136-2633C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000479770.2	n.*953-969G>A		intron_variant	Intron 5 of 5	1		ENSP00000436967.1
TIRAP-AS1	ENST00000524964.3	n.130-2687C>T		intron_variant	Intron 1 of 1	2
TIRAP-AS1	ENST00000691542.2	n.121-2633C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9740 AN: 151970 Hom.: 438 Cov.: 33

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0662

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

GnomAD4 genome AF: 0.0641 AC: 9753 AN: 152086 Hom.: 439 Cov.: 33 AF XY: 0.0680 AC XY: 5055 AN XY: 74342

African (AFR) AF: 0.0614 AC: 2545 AN: 41460

American (AMR) AF: 0.137 AC: 2099 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3470

East Asian (EAS) AF: 0.174 AC: 900 AN: 5170

South Asian (SAS) AF: 0.0795 AC: 383 AN: 4820

European-Finnish (FIN) AF: 0.0670 AC: 708 AN: 10566

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0414 AC: 2818 AN: 68010

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.0560 Hom.: 44

Bravo AF: 0.0672

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs8177387; hg19: chr11-126167184;