rs8177399

Variant names:

• chr11-126290931-C-G
• NM_001318777.2:c.37C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-126290931-C-G
• chr11-126290931-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001318777.2(TIRAP):​c.37C>G​(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIRAP NM_001318777.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051250458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIRAP	NM_001318777.2	c.37C>G	p.Arg13Gly	missense_variant	Exon 3 of 5	ENST00000392679.6	NP_001305706.1
TIRAP	NM_001318776.2	c.37C>G	p.Arg13Gly	missense_variant	Exon 3 of 4		NP_001305705.1
TIRAP	NM_148910.3	c.37C>G	p.Arg13Gly	missense_variant	Exon 4 of 5		NP_683708.1
TIRAP	NM_001039661.2	c.37C>G	p.Arg13Gly	missense_variant	Exon 4 of 6		NP_001034750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000392679.6	c.37C>G	p.Arg13Gly	missense_variant	Exon 3 of 5	2	NM_001318777.2	ENSP00000376446.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.085	T;.;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.62	.;T;.
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.051	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.084
Sift	Uncertain	0.021	D;D;D
Sift4G	Uncertain	0.059	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.097
MutPred		0.18		Loss of MoRF binding (P = 0.0109);Loss of MoRF binding (P = 0.0109);Loss of MoRF binding (P = 0.0109);
MVP		0.41
MPC		0.043
ClinPred		0.11	T
GERP RS		0.90
Varity_R		0.095
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-126160826;