dbSNP rs7657186: TLR3:c.-8+3637G>A (chr4-186072885-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+3637G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,164 control chromosomes in the GnomAD database, including 3,649 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 ( 3649 hom., cov: 33)

Consequence

TLR3
NM_003265.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.638

Publications

22 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=-1.02).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR3	NM_003265.3 link	c.-8+3637G>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+3637G>A	intron_variant	Intron 1 of 4	1	NM_003265.3	ENSP00000296795.3	O15455-1
TLR3	ENST00000513189.1 link	n.-8+3637G>A	intron_variant	Intron 1 of 4	1		ENSP00000423386.1	D6RA51
TLR3	ENST00000698351.1 link	c.-8+3637G>A	intron_variant	Intron 1 of 4			ENSP00000513674.1	A0A8V8TLN9
TLR3	ENST00000698352.1 link	n.-8+3637G>A	intron_variant	Intron 1 of 4			ENSP00000513675.1	A0A8V8TN43

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32605

AN:

152046

Hom.:

3644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.228

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

GnomAD4 genome

AF:

0.214

AC:

32627

AN:

152164

Hom.:

3649

Cov.:

AF XY:

0.210

AC XY:

15609

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.240

AC:

9952

AN:

41498

American (AMR)

AF:

0.186

AC:

2842

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1149

AN:

3466

East Asian (EAS)

AF:

0.131

AC:

681

AN:

5180

South Asian (SAS)

AF:

0.248

AC:

1195

AN:

4826

European-Finnish (FIN)

AF:

0.133

AC:

1407

AN:

10596

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14649

AN:

67994

Other (OTH)

AF:

0.231

AC:

487

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1334

2667

4001

5334

6668

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:

0.219

Hom.:

15706

Bravo

AF:

0.219

Asia WGS

AF:

0.195

AC:

680

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.49

(source)

DANN

Benign

0.34

PhyloP100

-0.64

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