rs142475083

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001318777.2(TIRAP):​c.393C>G​(p.Ser131Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TIRAP
NM_001318777.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.82
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP7
Synonymous conserved (PhyloP=-3.82 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TIRAPNM_001318777.2 linkc.393C>G p.Ser131Ser synonymous_variant Exon 4 of 5 ENST00000392679.6 NP_001305706.1 P58753-1A0A024R3M4
TIRAPNM_001318776.2 linkc.393C>G p.Ser131Ser synonymous_variant Exon 4 of 4 NP_001305705.1 P58753-2
TIRAPNM_148910.3 linkc.393C>G p.Ser131Ser synonymous_variant Exon 5 of 5 NP_683708.1 P58753-2
TIRAPNM_001039661.2 linkc.393C>G p.Ser131Ser synonymous_variant Exon 5 of 6 NP_001034750.1 P58753-1A0A024R3M4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TIRAPENST00000392679.6 linkc.393C>G p.Ser131Ser synonymous_variant Exon 4 of 5 2 NM_001318777.2 ENSP00000376446.1 P58753-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.018
DANN
Benign
0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142475083; hg19: chr11-126162697; API