rs609634

Variant names:

• chr11-126293229-C-T
• rs609634
• ENST00000392678.7:c.*112C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-126293229-C-T
• chr11-126293229-C-A
• chr11-126293229-C-G

Variant summary

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

The ENST00000392678.7(TIRAP):​c.*112C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 1,232,986 control chromosomes in the GnomAD database, including 377,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (41951 hom., cov: 32)
  • Exomes 𝑓: 0.79 (335770 hom.)
• Consequence: TIRAP ENST00000392678.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42
• Publications: 13 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]

ENSG00000254905 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-126293229-C-T is Benign according to our data. Variant chr11-126293229-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392678.7. 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.646+174C>T		intron	N/A	NP_001305706.1	P58753-1
	TIRAP	NM_001039661.2		c.646+174C>T		intron	N/A	NP_001034750.1	P58753-1
	TIRAP	NM_001318776.2		c.*112C>T		downstream_gene	N/A	NP_001305705.1	P58753-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIRAP	ENST00000392678.7	TSL:1	c.*112C>T		3_prime_UTR	Exon 5 of 5	ENSP00000376445.3	P58753-2
	TIRAP	ENST00000392679.6	TSL:2 MANE Select	c.646+174C>T		intron	N/A	ENSP00000376446.1	P58753-1
	TIRAP	ENST00000392680.6	TSL:1	c.646+174C>T		intron	N/A	ENSP00000376447.2	P58753-1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111400 AN: 151928 Hom.: 41915 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.786 AC: 849810 AN: 1080940 Hom.: 335770 Cov.: 14 AF XY: 0.790 AC XY: 430528 AN XY: 544930

African (AFR) AF: 0.554 AC: 13982 AN: 25218

American (AMR) AF: 0.846 AC: 28509 AN: 33680

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 17083 AN: 22550

East Asian (EAS) AF: 1.00 AC: 34472 AN: 34488

South Asian (SAS) AF: 0.881 AC: 63285 AN: 71838

European-Finnish (FIN) AF: 0.779 AC: 26452 AN: 33940

Middle Eastern (MID) AF: 0.715 AC: 3613 AN: 5050

European-Non Finnish (NFE) AF: 0.775 AC: 625163 AN: 806366

Other (OTH) AF: 0.779 AC: 37251 AN: 47810

GnomAD4 genome AF: 0.733 AC: 111489 AN: 152046 Hom.: 41951 Cov.: 32 AF XY: 0.743 AC XY: 55227 AN XY: 74304

African (AFR) AF: 0.567 AC: 23493 AN: 41418

American (AMR) AF: 0.802 AC: 12266 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2610 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5149 AN: 5156

South Asian (SAS) AF: 0.889 AC: 4290 AN: 4824

European-Finnish (FIN) AF: 0.800 AC: 8473 AN: 10586

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52742 AN: 67988

Other (OTH) AF: 0.730 AC: 1545 AN: 2116

Alfa AF: 0.739 Hom.: 5741

Bravo AF: 0.723

Asia WGS AF: 0.926 AC: 3219 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	0.28
DANN	Benign	0.62
PhyloP100		-1.4
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: rs609634; hg19: chr11-126163124;