chr4-38798593-C-G

Variant names:

Variant summary

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

The NM_003263.4(TLR1):c.239G>C(p.Arg80Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,613,772 control chromosomes in the GnomAD database, including 7,073 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 (no stars).

Frequency

Genomes: 𝑓 0.069 ( 790 hom., cov: 32)

Exomes 𝑓: 0.080 ( 6283 hom. )

Consequence

TLR1
NM_003263.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.117

Publications

105 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=0.002158165).

BP6

Variant 4-38798593-C-G is Benign according to our data. Variant chr4-38798593-C-G is described in ClinVar as Benign. ClinVar VariationId is 3037177.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4 link	c.239G>C	p.Arg80Thr	missense_variant	Exon 4 of 4	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7 link	c.239G>C	p.Arg80Thr	missense_variant	Exon 4 of 4	1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes

AF:

0.0692

AC:

10523

AN:

152044

Hom.:

790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0417

GnomAD2 exomes

AF:

0.0694

AC:

17406

AN:

250914

AF XY:

0.0683

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.0434

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.0933

Gnomad OTH exome

AF:

0.0673

GnomAD4 exome

AF:

0.0805

AC:

117604

AN:

1461610

Hom.:

6283

Cov.:

AF XY:

0.0791

AC XY:

57502

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.0109

AC:

364

AN:

33474

American (AMR)

AF:

0.0209

AC:

934

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0442

AC:

1154

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.00332

AC:

286

AN:

86228

European-Finnish (FIN)

AF:

0.220

AC:

11753

AN:

53402

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0891

AC:

99050

AN:

1111814

Other (OTH)

AF:

0.0667

AC:

4027

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

6255

12510

18764

25019

31274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3280

6560

9840

13120

16400

<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:

0.0692

AC:

10522

AN:

152162

Hom.:

790

Cov.:

AF XY:

0.0718

AC XY:

5341

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0130

AC:

542

AN:

41536

American (AMR)

AF:

0.0215

AC:

328

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00249

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.238

AC:

2509

AN:

10538

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6810

AN:

68008

Other (OTH)

AF:

0.0413

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

456

912

1369

1825

2281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0852

Hom.:

558

Bravo

AF:

0.0492

TwinsUK

AF:

0.0885

AC:

328

ALSPAC

AF:

0.0737

AC:

284

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.0908

AC:

781

ExAC

AF:

0.0687

AC:

8341

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0850

EpiControl

AF:

0.0767

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TLR1-related disorder

Benign:1

Dec 05, 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.066

T;T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.84

T;.;D;D

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.7

L;L;.;.

PhyloP100

0.12

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

D;D;D;D

REVEL

Benign

0.14

Sift

Benign

0.042

D;D;D;D

Sift4G

Benign

0.46

T;T;T;.

Polyphen

0.13

B;B;.;.

Vest4

0.11

MPC

0.12

ClinPred

0.014

GERP RS

3.2

Varity_R

0.35

gMVP

0.23

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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