11-126290792-A-C

Variant names:

• chr11-126290792-A-C
• rs1893352
• NM_001318777.2:c.-92-11A>C

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.-92-11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,504,330 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: TIRAP NM_001318777.2 intron
• Scores: Splicing: ADA: 0.00003446
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 26 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=-0.81).

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.-92-11A>C		intron	N/A	NP_001305706.1
	TIRAP	NM_001318776.2		c.-92-11A>C		intron	N/A	NP_001305705.1
	TIRAP	NM_148910.3		c.-92-11A>C		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.-92-11A>C		intron	N/A	ENSP00000376446.1
	TIRAP	ENST00000392678.7	TSL:1	c.-92-11A>C		intron	N/A	ENSP00000376445.3
	TIRAP	ENST00000392680.6	TSL:1	c.-92-11A>C		intron	N/A	ENSP00000376447.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151986 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000296 AC: 4 AN: 1352344 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 666936

African (AFR) AF: 0.00 AC: 0 AN: 28662

American (AMR) AF: 0.00 AC: 0 AN: 22058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22804

East Asian (EAS) AF: 0.00 AC: 0 AN: 34232

South Asian (SAS) AF: 0.00 AC: 0 AN: 72212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1062782

Other (OTH) AF: 0.0000358 AC: 2 AN: 55898

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151986 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74204

African (AFR) AF: 0.00 AC: 0 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000127 Hom.: 834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.7
DANN	Benign	0.48
PhyloP100		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.0020
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: rs1893352; hg19: chr11-126160687;