11-126289139-C-T

Variant names:

• chr11-126289139-C-T
• rs646005
• NM_001318777.2:c.-216-1323C>T

Variant summary

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

The NM_001318777.2(TIRAP):​c.-216-1323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,118 control chromosomes in the GnomAD database, including 27,983 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 0.60 (27983 hom., cov: 33)
• Consequence: TIRAP NM_001318777.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

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.-216-1323C>T		intron	N/A	NP_001305706.1	P58753-1
	TIRAP	NM_001318776.2		c.-216-1323C>T		intron	N/A	NP_001305705.1	P58753-2
	TIRAP	NM_148910.3		c.-385-526C>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.-216-1323C>T		intron	N/A	ENSP00000376446.1	P58753-1
	TIRAP	ENST00000392678.7	TSL:1	c.-385-526C>T		intron	N/A	ENSP00000376445.3	P58753-2
	TIRAP	ENST00000392680.6	TSL:1	c.-369-526C>T		intron	N/A	ENSP00000376447.2	P58753-1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90523 AN: 152000 Hom.: 27954 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.596 AC: 90591 AN: 152118 Hom.: 27983 Cov.: 33 AF XY: 0.606 AC XY: 45049 AN XY: 74352

African (AFR) AF: 0.472 AC: 19554 AN: 41456

American (AMR) AF: 0.691 AC: 10561 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3470

East Asian (EAS) AF: 0.978 AC: 5078 AN: 5192

South Asian (SAS) AF: 0.716 AC: 3455 AN: 4824

European-Finnish (FIN) AF: 0.658 AC: 6947 AN: 10564

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41153 AN: 68012

Other (OTH) AF: 0.586 AC: 1238 AN: 2114

Alfa AF: 0.572 Hom.: 4048

Bravo AF: 0.590

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.26
PhyloP100		-0.089
Mutation Taster		=100/0	polymorphism (auto)

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: rs646005; hg19: chr11-126159034;