Variant rs5743610 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The ENST00000308979.7(TLR1):c.114C>T(p.His38=) 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
ENST00000308979.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.162

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 made for transcript

Verdict is Benign. Variant got -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 ClinVar 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2677 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	NM_003263.4 linkuse as main transcript	c.114C>T	p.His38=	synonymous_variant	4/4	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7 linkuse as main transcript	c.114C>T	p.His38=	synonymous_variant	4/4	1	NM_003263.4	ENSP00000354932	P1

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

GnomAD3 exomes

AF:

0.0205

AC:

5139

AN:

250194

Hom.:

AF XY:

0.0211

AC XY:

2861

AN XY:

135628

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 SAS exome

AF:

0.00890

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

Gnomad4 AFR exome

AF:

0.00415

Gnomad4 AMR exome

AF:

0.0139

Gnomad4 ASJ exome

AF:

0.0330

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00936

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.0270

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0176

AC:

2677

AN:

152280

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1266

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00459

Gnomad4 AMR

AF:

0.0206

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00766

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0266

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0266

Hom.:

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

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

DANN

Benign

0.38

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