chr11-126292573-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001318777.2(TIRAP):c.164G>A(p.Ser55Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,613,986 control chromosomes in the GnomAD database, including 3,252 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.062 ( 417 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2835 hom. )

Consequence

TIRAP
NM_001318777.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.473

Publications

37 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0012226701).

BP6

Variant 11-126292573-G-A is Benign according to our data. Variant chr11-126292573-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688471.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TIRAP	NM_001318777.2	MANE Select	c.164G>A	p.Ser55Asn	missense	Exon 4 of 5	NP_001305706.1
TIRAP	NM_001318776.2		c.164G>A	p.Ser55Asn	missense	Exon 4 of 4	NP_001305705.1
TIRAP	NM_148910.3		c.164G>A	p.Ser55Asn	missense	Exon 5 of 5	NP_683708.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TIRAP	ENST00000392679.6	TSL:2 MANE Select	c.164G>A	p.Ser55Asn	missense	Exon 4 of 5	ENSP00000376446.1
TIRAP	ENST00000392678.7	TSL:1	c.164G>A	p.Ser55Asn	missense	Exon 5 of 5	ENSP00000376445.3
TIRAP	ENST00000392680.6	TSL:1	c.164G>A	p.Ser55Asn	missense	Exon 5 of 6	ENSP00000376447.2

Frequencies

GnomAD3 genomes

AF:

0.0620

AC:

9420

AN:

152056

Hom.:

416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.0802

Gnomad FIN

AF:

0.0665

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0413

Gnomad OTH

AF:

0.0647

GnomAD2 exomes

AF:

0.0776

AC:

19476

AN:

251124

AF XY:

0.0726

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.0368

Gnomad EAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.0687

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0496

AC:

72462

AN:

1461812

Hom.:

2835

Cov.:

AF XY:

0.0498

AC XY:

36231

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.0562

AC:

1881

AN:

33478

American (AMR)

AF:

0.179

AC:

7989

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0376

AC:

982

AN:

26134

East Asian (EAS)

AF:

0.168

AC:

6671

AN:

39694

South Asian (SAS)

AF:

0.0704

AC:

6069

AN:

86252

European-Finnish (FIN)

AF:

0.0679

AC:

3625

AN:

53414

Middle Eastern (MID)

AF:

0.0472

AC:

272

AN:

5766

European-Non Finnish (NFE)

AF:

0.0375

AC:

41745

AN:

1111980

Other (OTH)

AF:

0.0534

AC:

3228

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

5011

10022

15034

20045

25056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1706

3412

5118

6824

8530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0620

AC:

9433

AN:

152174

Hom.:

417

Cov.:

AF XY:

0.0657

AC XY:

4890

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0547

AC:

2272

AN:

41516

American (AMR)

AF:

0.137

AC:

2085

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3472

East Asian (EAS)

AF:

0.171

AC:

884

AN:

5160

South Asian (SAS)

AF:

0.0790

AC:

381

AN:

4820

European-Finnish (FIN)

AF:

0.0665

AC:

705

AN:

10596

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0413

AC:

2809

AN:

68022

Other (OTH)

AF:

0.0654

AC:

138

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

430

860

1289

1719

2149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0482

Hom.:

1079

Bravo

AF:

0.0651

TwinsUK

AF:

0.0372

AC:

138

ALSPAC

AF:

0.0420

AC:

162

ESP6500AA

AF:

0.0618

AC:

272

ESP6500EA

AF:

0.0370

AC:

318

ExAC

AF:

0.0733

AC:

8899

Asia WGS

AF:

0.143

AC:

497

AN:

3478

EpiCase

AF:

0.0395

EpiControl

AF:

0.0397

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

TIRAP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.5

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.15

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

PhyloP100

0.47

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.86

REVEL

Benign

0.086

Sift

Benign

0.88

Sift4G

Benign

0.39

Polyphen

0.0030

Vest4

0.025

MPC

0.027

ClinPred

0.00084

GERP RS

-2.1

Varity_R

0.044

gMVP

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over