rs5743816

Positions:

chr4-38828081-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000508254.6(TLR6):c.1393G>A(p.Val465Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,613,944 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.023 ( 160 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 146 hom. )

Consequence

TLR6
ENST00000508254.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.405

Variant links:

Genes affected

TLR6 (HGNC:16711): (toll like receptor 6) 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 receptor functionally interacts with toll-like receptor 2 to mediate cellular response to bacterial lipoproteins. A Ser249Pro polymorphism in the extracellular domain of the encoded protein may be associated with an increased of asthma is some populations.[provided by RefSeq, Jan 2011]

TLR6 links:

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012029707).

BP6

Variant 4-38828081-C-T is Benign according to our data. Variant chr4-38828081-C-T is described in ClinVar as [Benign]. Clinvar id is 791975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR6	NM_006068.5 linkuse as main transcript	c.1393G>A	p.Val465Ile	missense_variant	2/2	ENST00000508254.6	NP_006059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR6	ENST00000508254.6 linkuse as main transcript	c.1393G>A	p.Val465Ile	missense_variant	2/2	1	NM_006068.5	ENSP00000424718	P1	Q9Y2C9-1
TLR6	ENST00000381950.2 linkuse as main transcript	c.1393G>A	p.Val465Ile	missense_variant	3/3			ENSP00000371376	P1	Q9Y2C9-1
TLR1	ENST00000506146.5 linkuse as main transcript	c.-352-22888G>A		intron_variant		4		ENSP00000423725

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3554

AN:

152160

Hom.:

156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0771

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.00830

AC:

2087

AN:

251366

Hom.:

AF XY:

0.00735

AC XY:

999

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0755

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00571

Gnomad SAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00383

AC:

5597

AN:

1461666

Hom.:

146

Cov.:

AF XY:

0.00395

AC XY:

2870

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0788

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00501

Gnomad4 SAS exome

AF:

0.0166

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000571

Gnomad4 OTH exome

AF:

0.00795

GnomAD4 genome

AF:

0.0235

AC:

3574

AN:

152278

Hom.:

160

Cov.:

AF XY:

0.0239

AC XY:

1777

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0772

Gnomad4 AMR

AF:

0.00987

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00521

Gnomad4 SAS

AF:

0.0188

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0979

Hom.:

3222

Bravo

AF:

0.0257

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.00995

AC:

1208

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.1

DANN

Benign

0.69

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.55

T;.

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.7

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.27

N;N

REVEL

Benign

0.018

Sift

Benign

1.0

T;T

Sift4G

Benign

0.97

T;T

Polyphen

0.0

B;B

Vest4

0.064

MVP

0.20

MPC

0.12

ClinPred

0.00040

GERP RS

2.6

Varity_R

0.012

gMVP

0.051

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