Variant 11-126291595-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.832

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]

TIRAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TIRAP	NM_001318777.2 link	c.67+634T>C	intron_variant	Intron 3 of 4	ENST00000392679.6	NP_001305706.1	P58753-1A0A024R3M4
TIRAP	NM_001318776.2 link	c.67+634T>C	intron_variant	Intron 3 of 3		NP_001305705.1	P58753-2
TIRAP	NM_148910.3 link	c.67+634T>C	intron_variant	Intron 4 of 4		NP_683708.1	P58753-2
TIRAP	NM_001039661.2 link	c.67+634T>C	intron_variant	Intron 4 of 5		NP_001034750.1	P58753-1A0A024R3M4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000392679.6 link	c.67+634T>C		intron_variant	Intron 3 of 4	2	NM_001318777.2	ENSP00000376446.1		P58753-1

Frequencies

GnomAD3 genomes

AF:

0.729

AC:

110691

AN:

151814

Hom.:

41551

Cov.:

show subpopulations

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.:

AF XY:

0.801

AC XY:

140999

AN XY:

176088

show subpopulations

Gnomad4 AFR exome

AF:

0.552

Gnomad4 AMR exome

AF:

0.854

Gnomad4 ASJ exome

AF:

0.736

Gnomad4 EAS exome

AF:

0.990

Gnomad4 SAS exome

AF:

0.864

Gnomad4 FIN exome

AF:

0.779

Gnomad4 NFE exome

AF:

0.768

Gnomad4 OTH exome

AF:

0.771

GnomAD4 genome

AF:

0.729

AC:

110778

AN:

151930

Hom.:

41587

Cov.:

AF XY:

0.739

AC XY:

54878

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.562

Gnomad4 AMR

AF:

0.801

Gnomad4 ASJ

AF:

0.731

Gnomad4 EAS

AF:

0.991

Gnomad4 SAS

AF:

0.870

Gnomad4 FIN

AF:

0.799

Gnomad4 NFE

AF:

0.773

Gnomad4 OTH

AF:

0.723

Alfa

AF:

0.735

Hom.:

5601

Bravo

AF:

0.719

Asia WGS

AF:

0.912

AC:

3171

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.048

DANN

Benign

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over