dbSNP rs5743688: TLR2:c.-162-1686G>A (chr4-153686216-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_001318789.2(TLR2):c.-162-1686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 152,152 control chromosomes in the GnomAD database, including 689 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 0.082 ( 689 hom., cov: 32)

Consequence

TLR2
NM_001318789.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.146

Publications

2 publications found

Variant links:

Genes affected

TLR2 (HGNC:11848): (toll like receptor 2) 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. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host's inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TLR2 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318789.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR2	NM_001318789.2	MANE Select	c.-162-1686G>A	intron	N/A	NP_001305718.1	O60603
TLR2	NM_001318787.2		c.-372-1701G>A	intron	N/A	NP_001305716.1	A0A0S2Z4S4
TLR2	NM_001318790.2		c.-162-1686G>A	intron	N/A	NP_001305719.1	A0A0S2Z4S4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR2	ENST00000642700.2	MANE Select	c.-162-1686G>A	intron	N/A	ENSP00000494425.1	O60603
TLR2	ENST00000260010.7	TSL:6	c.-1554-1686G>A	intron	N/A	ENSP00000260010.6	O60603
TLR2	ENST00000642580.1		c.-88-1701G>A	intron	N/A	ENSP00000495339.1	O60603

Frequencies

GnomAD3 genomes

AF:

0.0820

AC:

12466

AN:

152034

Hom.:

689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.0972

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0755

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

GnomAD4 genome

AF:

0.0819

AC:

12463

AN:

152152

Hom.:

689

Cov.:

AF XY:

0.0851

AC XY:

6327

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0174

AC:

723

AN:

41526

American (AMR)

AF:

0.104

AC:

1592

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

469

AN:

3470

East Asian (EAS)

AF:

0.00328

AC:

AN:

5178

South Asian (SAS)

AF:

0.0977

AC:

470

AN:

4812

European-Finnish (FIN)

AF:

0.170

AC:

1794

AN:

10566

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7107

AN:

67984

Other (OTH)

AF:

0.0747

AC:

158

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

565

1130

1695

2260

2825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0334

Hom.:

Bravo

AF:

0.0724

Asia WGS

AF:

0.0430

AC:

154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.0

(source)

DANN

Benign

0.48

PhyloP100

0.15

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over