11-126291595-T-C

Variant names:

• chr11-126291595-T-C
• rs614700
• NM_001318777.2:c.67+634T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001318777.2(TIRAP):​c.67+634T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 462,890 control chromosomes in the GnomAD database, including 140,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (41587 hom., cov: 33)
  • Exomes 𝑓: 0.79 (98951 hom.)
• Consequence: TIRAP NM_001318777.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.832
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-126291595-T-C is Benign according to our data. Variant chr11-126291595-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688416.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 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.67+634T>C		intron	N/A	NP_001305706.1	P58753-1
	TIRAP	NM_001318776.2		c.67+634T>C		intron	N/A	NP_001305705.1	P58753-2
	TIRAP	NM_148910.3		c.67+634T>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.67+634T>C		intron	N/A	ENSP00000376446.1	P58753-1
	TIRAP	ENST00000392678.7	TSL:1	c.67+634T>C		intron	N/A	ENSP00000376445.3	P58753-2
	TIRAP	ENST00000392680.6	TSL:1	c.67+634T>C		intron	N/A	ENSP00000376447.2	P58753-1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110691 AN: 151814 Hom.: 41551 Cov.: 33

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.720

GnomAD4 exome AF: 0.793 AC: 246731 AN: 310960 Hom.: 98951 Cov.: 4 AF XY: 0.801 AC XY: 140999 AN XY: 176088

African (AFR) AF: 0.552 AC: 4806 AN: 8708

American (AMR) AF: 0.854 AC: 23233 AN: 27198

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 7707 AN: 10466

East Asian (EAS) AF: 0.990 AC: 9154 AN: 9244

South Asian (SAS) AF: 0.864 AC: 51283 AN: 59384

European-Finnish (FIN) AF: 0.779 AC: 9545 AN: 12254

Middle Eastern (MID) AF: 0.701 AC: 1942 AN: 2772

European-Non Finnish (NFE) AF: 0.768 AC: 127933 AN: 166496

Other (OTH) AF: 0.771 AC: 11128 AN: 14438

GnomAD4 genome AF: 0.729 AC: 110778 AN: 151930 Hom.: 41587 Cov.: 33 AF XY: 0.739 AC XY: 54878 AN XY: 74274

African (AFR) AF: 0.562 AC: 23200 AN: 41276

American (AMR) AF: 0.801 AC: 12241 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2536 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5125 AN: 5170

South Asian (SAS) AF: 0.870 AC: 4201 AN: 4828

European-Finnish (FIN) AF: 0.799 AC: 8469 AN: 10594

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.773 AC: 52561 AN: 68002

Other (OTH) AF: 0.723 AC: 1528 AN: 2112

Alfa AF: 0.728 Hom.: 5724

Bravo AF: 0.719

Asia WGS AF: 0.912 AC: 3171 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.048
DANN	Benign	0.29
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs614700; hg19: chr11-126161490;