11-126292326-A-T

Variant names:

• chr11-126292326-A-T
• rs595209
• NM_001318777.2:c.68-151A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001318777.2(TIRAP):​c.68-151A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000369 in 542,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: TIRAP NM_001318777.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 11 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318777.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	NM_001318777.2	MANE Select	c.68-151A>T		intron	N/A	NP_001305706.1	P58753-1
	TIRAP	NM_001318776.2		c.68-151A>T		intron	N/A	NP_001305705.1	P58753-2
	TIRAP	NM_148910.3		c.68-151A>T		intron	N/A	NP_683708.1	P58753-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	ENST00000392679.6	TSL:2 MANE Select	c.68-151A>T		intron	N/A	ENSP00000376446.1	P58753-1
	TIRAP	ENST00000392678.7	TSL:1	c.68-151A>T		intron	N/A	ENSP00000376445.3	P58753-2
	TIRAP	ENST00000392680.6	TSL:1	c.68-151A>T		intron	N/A	ENSP00000376447.2	P58753-1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000369 AC: 2 AN: 542182 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 280468

African (AFR) AF: 0.00 AC: 0 AN: 13952

American (AMR) AF: 0.00 AC: 0 AN: 18604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13994

East Asian (EAS) AF: 0.0000321 AC: 1 AN: 31194

South Asian (SAS) AF: 0.00 AC: 0 AN: 45558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2148

European-Non Finnish (NFE) AF: 0.00000279 AC: 1 AN: 358878

Other (OTH) AF: 0.00 AC: 0 AN: 28764

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.52
PhyloP100		0.12

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

Other links and lift over

dbSNP: rs595209; hg19: chr11-126162221;