Genetic Variant TLR2:c.-163+233C>T (chr4-153684593-C-T) – 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.-163+233C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,198 control chromosomes in the GnomAD database, including 5,778 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 0.26 ( 5778 hom., cov: 33)

Consequence

TLR2
NM_001318789.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

9 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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 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.-163+233C>T	intron	N/A	NP_001305718.1	O60603
TLR2	NM_001318787.2		c.-373+233C>T	intron	N/A	NP_001305716.1	A0A0S2Z4S4
TLR2	NM_001318790.2		c.-163+256C>T	intron	N/A	NP_001305719.1	A0A0S2Z4S4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR2	ENST00000642700.2	MANE Select	c.-163+233C>T	intron	N/A	ENSP00000494425.1	O60603
TLR2	ENST00000260010.7	TSL:6	c.-1555+233C>T	intron	N/A	ENSP00000260010.6	O60603
TLR2	ENST00000642580.1		c.-89+233C>T	intron	N/A	ENSP00000495339.1	O60603

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39724

AN:

152080

Hom.:

5777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.289

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

GnomAD4 genome

AF:

0.261

AC:

39732

AN:

152198

Hom.:

5778

Cov.:

AF XY:

0.257

AC XY:

19157

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.133

AC:

5510

AN:

41554

American (AMR)

AF:

0.224

AC:

3424

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

958

AN:

3468

East Asian (EAS)

AF:

0.273

AC:

1408

AN:

5156

South Asian (SAS)

AF:

0.163

AC:

790

AN:

4832

European-Finnish (FIN)

AF:

0.362

AC:

3833

AN:

10598

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.337

AC:

22914

AN:

67968

Other (OTH)

AF:

0.289

AC:

610

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1503

3006

4510

6013

7516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.319

Hom.:

20239

Bravo

AF:

0.249

Asia WGS

AF:

0.208

AC:

722

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.0

(source)

DANN

Benign

0.78

PhyloP100

-1.9

PromoterAI

0.018

Neutral

(source)

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