dbSNP rs13126816: TLR3:c.-7-3589G>A (chr4-186073024-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003265.3(TLR3):c.-7-3589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,168 control chromosomes in the GnomAD database, including 3,602 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3602 hom., cov: 33)

Consequence

TLR3
NM_003265.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.336

Publications

34 publications found

Variant links:

Genes affected

TLR3 (HGNC:11849): (toll like receptor 3) 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 is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It thus plays a role in host defense against multiple viruses. [provided by RefSeq, Jul 2021]

TLR3 Gene-Disease associations (from GenCC):

immunodeficiency 83, susceptibility to viral infections
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TLR3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3 link	c.-7-3589G>A		intron_variant	Intron 1 of 4	ENST00000296795.8	NP_003256.1	O15455-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TLR3	ENST00000296795.8 link	c.-7-3589G>A	intron_variant	Intron 1 of 4	1	NM_003265.3	ENSP00000296795.3	O15455-1
TLR3	ENST00000513189.1 link	n.-7-3589G>A	intron_variant	Intron 1 of 4	1		ENSP00000423386.1	D6RA51
TLR3	ENST00000698351.1 link	c.-7-3589G>A	intron_variant	Intron 1 of 4			ENSP00000513674.1	A0A8V8TLN9
TLR3	ENST00000698352.1 link	n.-7-3589G>A	intron_variant	Intron 1 of 4			ENSP00000513675.1	A0A8V8TN43

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31506

AN:

152050

Hom.:

3599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.207

AC:

31526

AN:

152168

Hom.:

3602

Cov.:

AF XY:

0.208

AC XY:

15479

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.115

AC:

4769

AN:

41534

American (AMR)

AF:

0.277

AC:

4234

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

521

AN:

3468

East Asian (EAS)

AF:

0.196

AC:

1014

AN:

5182

South Asian (SAS)

AF:

0.239

AC:

1155

AN:

4824

European-Finnish (FIN)

AF:

0.239

AC:

2525

AN:

10572

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16569

AN:

67982

Other (OTH)

AF:

0.235

AC:

498

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1270

2541

3811

5082

6352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.230

Hom.:

16878

Bravo

AF:

0.203

Asia WGS

AF:

0.199

AC:

692

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.1

(source)

DANN

Benign

0.71

PhyloP100

0.34

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over