rs8177387

Positions:

• chr11-126297289-G-A

Variant summary

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

The XR_948146.4(TIRAP-AS1):​n.2502C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 152,086 control chromosomes in the GnomAD database, including 439 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 0.064 (439 hom., cov: 33)
• Consequence: TIRAP-AS1 XR_948146.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

Genes affected

TIRAP-AS1 (HGNC:56069): (TIRAP antisense RNA 1)

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIRAP-AS1	XR_948146.4	n.2502C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000479770.2	c.*953-969G>A		intron_variant, NMD_transcript_variant		1		ENSP00000436967
TIRAP-AS1	ENST00000524964.2	n.117-2687C>T		intron_variant, non_coding_transcript_variant		2
TIRAP-AS1	ENST00000691542.1	n.115-2633C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9740 AN: 151970 Hom.: 438 Cov.: 33

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0662

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

GnomAD4 genome AF: 0.0641 AC: 9753 AN: 152086 Hom.: 439 Cov.: 33 AF XY: 0.0680 AC XY: 5055 AN XY: 74342

Gnomad4 AFR AF: 0.0614

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0670

Alfa AF: 0.0556 Hom.: 42

Bravo AF: 0.0672

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8177387; hg19: chr11-126167184;