rs3923647

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003263.4(TLR1):c.914A>T(p.His305Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,614,120 control chromosomes in the GnomAD database, including 836 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H305Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.038 ( 161 hom., cov: 32)

Exomes 𝑓: 0.027 ( 675 hom. )

Consequence

TLR1
NM_003263.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.91

Publications

42 publications found

Variant links:

Genes affected

TLR1 (HGNC:11847): (toll like receptor 1) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

TLR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024781823).

BP6

Variant 4-38797918-T-A is Benign according to our data. Variant chr4-38797918-T-A is described in ClinVar as Benign. ClinVar VariationId is 3056910.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4 link	c.914A>T	p.His305Leu	missense_variant	Exon 4 of 4	ENST00000308979.7	NP_003254.2	Q15399

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TLR1	ENST00000308979.7 link	c.914A>T	p.His305Leu	missense_variant	Exon 4 of 4	1	NM_003263.4	ENSP00000354932.2	Q15399
TLR1	ENST00000502213.7 link	c.914A>T	p.His305Leu	missense_variant	Exon 4 of 4	1		ENSP00000421259.1	Q15399
TLR1	ENST00000505744.6 link	n.235+2939A>T		intron_variant	Intron 3 of 3	3
TLR1	ENST00000510552.2 link	n.39-3290A>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5809

AN:

152174

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0728

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0292

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0273

Gnomad OTH

AF:

0.0425

GnomAD2 exomes

AF:

0.0273

AC:

6835

AN:

250542

AF XY:

0.0262

show subpopulations

Gnomad AFR exome

AF:

0.0781

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0663

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0270

GnomAD4 exome

AF:

0.0265

AC:

38768

AN:

1461828

Hom.:

675

Cov.:

AF XY:

0.0261

AC XY:

18965

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0737

AC:

2467

AN:

33480

American (AMR)

AF:

0.0175

AC:

782

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0623

AC:

1627

AN:

26134

East Asian (EAS)

AF:

0.000176

AC:

AN:

39696

South Asian (SAS)

AF:

0.00948

AC:

818

AN:

86256

European-Finnish (FIN)

AF:

0.0151

AC:

805

AN:

53392

Middle Eastern (MID)

AF:

0.0352

AC:

203

AN:

5768

European-Non Finnish (NFE)

AF:

0.0273

AC:

30354

AN:

1111986

Other (OTH)

AF:

0.0282

AC:

1705

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2281

4562

6843

9124

11405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1106

2212

3318

4424

5530

<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:

0.0382

AC:

5819

AN:

152292

Hom.:

161

Cov.:

AF XY:

0.0367

AC XY:

2736

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0728

AC:

3026

AN:

41550

American (AMR)

AF:

0.0291

AC:

446

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0576

AC:

200

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.00849

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0136

AC:

144

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0273

AC:

1854

AN:

68008

Other (OTH)

AF:

0.0421

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

284

568

853

1137

1421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0192

Hom.:

Bravo

AF:

0.0405

TwinsUK

AF:

0.0294

AC:

109

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.0740

AC:

326

ESP6500EA

AF:

0.0313

AC:

269

ExAC

AF:

0.0295

AC:

3587

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0268

EpiControl

AF:

0.0293

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TLR1-related disorder

Benign:1

Oct 31, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.35

T;.

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;M

PhyloP100

1.9

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.079

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

0.017

B;B

Vest4

0.085

MPC

0.076

ClinPred

0.048

GERP RS

4.8

Varity_R

0.25

gMVP

0.43

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over