NM_003263.4:c.1938C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003263.4(TLR1):c.1938C>T(p.His646His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,614,132 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 127 hom. )

Consequence

TLR1
NM_003263.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.96

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-38796894-G-A is Benign according to our data. Variant chr4-38796894-G-A is described in ClinVar as [Benign]. Clinvar id is 779876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4 link	c.1938C>T	p.His646His	synonymous_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.1938C>T	p.His646His	synonymous_variant	Exon 4 of 4	1	NM_003263.4	ENSP00000354932.2	Q15399
TLR1	ENST00000502213.6 link	c.1938C>T	p.His646His	synonymous_variant	Exon 3 of 3	1		ENSP00000421259.1	Q15399
TLR1	ENST00000505744.5 link	n.235+3963C>T		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00408

AC:

621

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0982

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00862

AC:

2166

AN:

251402

Hom.:

AF XY:

0.00784

AC XY:

1065

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00317

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.00717

GnomAD4 exome

AF:

0.00283

AC:

4130

AN:

1461890

Hom.:

127

Cov.:

AF XY:

0.00275

AC XY:

2003

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00275

Gnomad4 EAS exome

AF:

0.0775

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00755

GnomAD4 genome

AF:

0.00408

AC:

621

AN:

152242

Hom.:

Cov.:

AF XY:

0.00469

AC XY:

349

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0982

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000718

Hom.:

Bravo

AF:

0.00465

Asia WGS

AF:

0.0530

AC:

183

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

TLR1-related disorder

Benign:1

Aug 16, 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

-0.87

CADD

Benign

0.14

DANN

Benign

0.30

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