rs5743610

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_003263.4(TLR1):c.114C>T(p.His38His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,613,594 control chromosomes in the GnomAD database, including 555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.018 ( 39 hom., cov: 32)

Exomes 𝑓: 0.024 ( 516 hom. )

Consequence

TLR1
NM_003263.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.162

Publications

10 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-38798718-G-A is Benign according to our data. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-38798718-G-A is described in CliVar as Benign. Clinvar id is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.162 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0176 (2677/152280) while in subpopulation NFE AF = 0.0266 (1809/68012). AF 95% confidence interval is 0.0256. There are 39 homozygotes in GnomAd4. There are 1266 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2677 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4 link	c.114C>T	p.His38His	synonymous_variant	Exon 4 of 4	ENST00000308979.7	NP_003254.2	Q15399

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7 link	c.114C>T	p.His38His	synonymous_variant	Exon 4 of 4	1	NM_003263.4	ENSP00000354932.2		Q15399

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2676

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00456

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0273

GnomAD2 exomes

AF:

0.0205

AC:

5139

AN:

250194

AF XY:

0.0211

show subpopulations

Gnomad AFR exome

AF:

0.00492

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0350

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.0310

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0237

AC:

34701

AN:

1461314

Hom.:

516

Cov.:

AF XY:

0.0235

AC XY:

17098

AN XY:

726950

show subpopulations

African (AFR)

AF:

0.00415

AC:

139

AN:

33470

American (AMR)

AF:

0.0139

AC:

622

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0330

AC:

861

AN:

26124

East Asian (EAS)

AF:

0.000403

AC:

AN:

39678

South Asian (SAS)

AF:

0.00936

AC:

807

AN:

86190

European-Finnish (FIN)

AF:

0.0151

AC:

804

AN:

53406

Middle Eastern (MID)

AF:

0.0294

AC:

163

AN:

5548

European-Non Finnish (NFE)

AF:

0.0270

AC:

30047

AN:

1111832

Other (OTH)

AF:

0.0206

AC:

1242

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

1730

3461

5191

6922

8652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1042

2084

3126

4168

5210

<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:

0.0176

AC:

2677

AN:

152280

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1266

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00459

AC:

191

AN:

41572

American (AMR)

AF:

0.0206

AC:

315

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3466

East Asian (EAS)

AF:

0.00116

AC:

AN:

5182

South Asian (SAS)

AF:

0.00766

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0136

AC:

144

AN:

10600

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0266

AC:

1809

AN:

68012

Other (OTH)

AF:

0.0270

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

146

291

437

582

728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0259

Hom.:

112

Bravo

AF:

0.0172

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0264

EpiControl

AF:

0.0279

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.64

(source)

DANN

Benign

0.38

PhyloP100

-0.16

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over