rs595209

Variant names:

• chr11-126292326-A-C
• rs595209
• NM_001318777.2:c.68-151A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-126292326-A-C
• chr11-126292326-A-G
• chr11-126292326-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	NM_001318777.2	MANE Select	c.68-151A>C		intron	N/A	NP_001305706.1	P58753-1
	TIRAP	NM_001318776.2		c.68-151A>C		intron	N/A	NP_001305705.1	P58753-2
	TIRAP	NM_148910.3		c.68-151A>C		intron	N/A	NP_683708.1	P58753-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	ENST00000392679.6	TSL:2 MANE Select	c.68-151A>C		intron	N/A	ENSP00000376446.1	P58753-1
	TIRAP	ENST00000392678.7	TSL:1	c.68-151A>C		intron	N/A	ENSP00000376445.3	P58753-2
	TIRAP	ENST00000392680.6	TSL:1	c.68-151A>C		intron	N/A	ENSP00000376447.2	P58753-1

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

African (AFR) AF: 0.0945 AC: 1317 AN: 13942

American (AMR) AF: 0.385 AC: 7153 AN: 18594

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 3406 AN: 13988

East Asian (EAS) AF: 0.637 AC: 19863 AN: 31172

South Asian (SAS) AF: 0.347 AC: 15803 AN: 45520

European-Finnish (FIN) AF: 0.248 AC: 7199 AN: 29072

Middle Eastern (MID) AF: 0.232 AC: 499 AN: 2148

European-Non Finnish (NFE) AF: 0.204 AC: 73124 AN: 358510

Other (OTH) AF: 0.254 AC: 7307 AN: 28738

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

African (AFR) AF: 0.0993 AC: 3875 AN: 39010

American (AMR) AF: 0.334 AC: 4785 AN: 14334

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 820 AN: 3392

East Asian (EAS) AF: 0.647 AC: 3170 AN: 4898

South Asian (SAS) AF: 0.360 AC: 1651 AN: 4588

European-Finnish (FIN) AF: 0.272 AC: 2186 AN: 8040

Middle Eastern (MID) AF: 0.239 AC: 65 AN: 272

European-Non Finnish (NFE) AF: 0.208 AC: 13668 AN: 65772

Other (OTH) AF: 0.226 AC: 445 AN: 1966

Alfa AF: 0.0989 Hom.: 173

Bravo AF: 0.217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.51
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs595209; hg19: chr11-126162221;