dbSNP rs11732384: TLR3:c.-8+2487G>A (chr4-186071735-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.-8+2487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,050 control chromosomes in the GnomAD database, including 1,353 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 0.12 ( 1353 hom., cov: 33)

Consequence

TLR3
NM_003265.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.578

Publications

6 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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3 link	c.-8+2487G>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.-8+2487G>A	intron_variant	Intron 1 of 4	1	NM_003265.3	ENSP00000296795.3	O15455-1
TLR3	ENST00000513189.1 link	n.-8+2487G>A	intron_variant	Intron 1 of 4	1		ENSP00000423386.1	D6RA51
TLR3	ENST00000698351.1 link	c.-8+2487G>A	intron_variant	Intron 1 of 4			ENSP00000513674.1	A0A8V8TLN9
TLR3	ENST00000698352.1 link	n.-8+2487G>A	intron_variant	Intron 1 of 4			ENSP00000513675.1	A0A8V8TN43

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17587

AN:

151932

Hom.:

1354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0335

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0787

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.0875

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

GnomAD4 genome

AF:

0.116

AC:

17580

AN:

152050

Hom.:

1353

Cov.:

AF XY:

0.120

AC XY:

8884

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0334

AC:

1387

AN:

41506

American (AMR)

AF:

0.106

AC:

1614

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0787

AC:

273

AN:

3468

East Asian (EAS)

AF:

0.196

AC:

1013

AN:

5176

South Asian (SAS)

AF:

0.103

AC:

497

AN:

4806

European-Finnish (FIN)

AF:

0.235

AC:

2475

AN:

10520

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10073

AN:

67968

Other (OTH)

AF:

0.0851

AC:

180

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

793

1586

2379

3172

3965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.129

Hom.:

214

Bravo

AF:

0.103

Asia WGS

AF:

0.135

AC:

468

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.40

(source)

DANN

Benign

0.64

PhyloP100

-0.58

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