chr11-126287084-C-T

Variant names:

• chr11-126287084-C-T
• rs595022
• NM_001318777.2:c.-216-3378C>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.-216-3378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,098 control chromosomes in the GnomAD database, including 5,577 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 0.24 (5577 hom., cov: 32)
• Consequence: TIRAP NM_001318777.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	NM_001318777.2	MANE Select	c.-216-3378C>T		intron	N/A	NP_001305706.1
	TIRAP	NM_001318776.2		c.-216-3378C>T		intron	N/A	NP_001305705.1
	TIRAP	NM_148910.3		c.-385-2581C>T		intron	N/A	NP_683708.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	ENST00000392679.6	TSL:2 MANE Select	c.-216-3378C>T		intron	N/A	ENSP00000376446.1
	TIRAP	ENST00000392678.7	TSL:1	c.-385-2581C>T		intron	N/A	ENSP00000376445.3
	TIRAP	ENST00000392680.6	TSL:1	c.-369-2581C>T		intron	N/A	ENSP00000376447.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36587 AN: 151980 Hom.: 5577 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.241 AC: 36587 AN: 152098 Hom.: 5577 Cov.: 32 AF XY: 0.253 AC XY: 18804 AN XY: 74342

African (AFR) AF: 0.0926 AC: 3843 AN: 41508

American (AMR) AF: 0.342 AC: 5224 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3472

East Asian (EAS) AF: 0.637 AC: 3298 AN: 5174

South Asian (SAS) AF: 0.369 AC: 1775 AN: 4816

European-Finnish (FIN) AF: 0.348 AC: 3672 AN: 10564

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17134 AN: 67968

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.229 Hom.: 1735

Bravo AF: 0.237

Asia WGS AF: 0.457 AC: 1585 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	1.6
DANN	Benign	0.43
PhyloP100		-0.68
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: rs595022; hg19: chr11-126156979;