Variant rs5743613 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003263.4(TLR1):c.944C>T(p.Pro315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000862 in 1,613,958 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

TLR1
NM_003263.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008791745).

BS2

High AC in GnomAd at 607 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR1	NM_003263.4 linkuse as main transcript	c.944C>T	p.Pro315Leu	missense_variant	4/4	ENST00000308979.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TLR1	ENST00000308979.7 linkuse as main transcript	c.944C>T	p.Pro315Leu	missense_variant	4/4	1	NM_003263.4	P1
TLR1	ENST00000502213.6 linkuse as main transcript	c.944C>T	p.Pro315Leu	missense_variant	3/3	1		P1
TLR1	ENST00000505744.5 linkuse as main transcript	n.235+2969C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00399

AC:

607

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00116

AC:

291

AN:

250610

Hom.:

AF XY:

0.000848

AC XY:

115

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000538

AC:

786

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000479

AC XY:

348

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0123

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00398

AC:

606

AN:

152276

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.00448

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00135

AC:

164

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.69

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.74

T;.

MetaRNN

Benign

0.0088

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.062

Sift

Benign

0.065

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.028

B;B

Vest4

0.38

MVP

0.51

MPC

0.19

ClinPred

0.021

GERP RS

0.73

Varity_R

0.13

gMVP

0.41

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over