rs595209

chr11-126292326-A-Cchr11-126292326-A-Gchr11-126292326-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318777.2(TIRAP):c.68-151A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 684,840 control chromosomes in the GnomAD database, including 25,066 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 0.22 (4318 hom., cov: 29)
  • Exomes 𝑓: 0.25 (20748 hom.)
• Consequence: TIRAP NM_001318777.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIRAP	NM_001318777.2	c.68-151A>C		intron_variant		ENST00000392679.6
TIRAP	NM_001039661.2	c.68-151A>C		intron_variant
TIRAP	NM_001318776.2	c.68-151A>C		intron_variant
TIRAP	NM_148910.3	c.68-151A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIRAP	ENST00000392679.6	c.68-151A>C		intron_variant		2	NM_001318777.2	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 30790 AN: 143112 Hom.: 4317 Cov.: 29

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.243

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.250 AC: 135671 AN: 541684 Hom.: 20748 AF XY: 0.255 AC XY: 71319 AN XY: 280216

Gnomad4 AFR exome AF: 0.0945

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.637

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.215 AC: 30790 AN: 143156 Hom.: 4318 Cov.: 29 AF XY: 0.227 AC XY: 15652 AN XY: 69092

Gnomad4 AFR AF: 0.0993

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.226

Alfa AF: 0.0987 Hom.: 165

Bravo AF: 0.217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.8
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs595209; hg19: chr11-126162221;