dbSNP rs4696480: TLR2:c.-163+1614T>A (chr4-153685974-T-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.-163+1614T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,038 control chromosomes in the GnomAD database, including 15,503 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 0.45 ( 15503 hom., cov: 32)

Consequence

TLR2
NM_001318789.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.435

Publications

191 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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 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+1614T>A	intron	N/A	NP_001305718.1	O60603
TLR2	NM_001318787.2		c.-373+1614T>A	intron	N/A	NP_001305716.1	A0A0S2Z4S4
TLR2	NM_001318790.2		c.-163+1637T>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.-163+1614T>A	intron	N/A	ENSP00000494425.1	O60603
TLR2	ENST00000260010.7	TSL:6	c.-1555+1614T>A	intron	N/A	ENSP00000260010.6	O60603
TLR2	ENST00000642580.1		c.-89+1614T>A	intron	N/A	ENSP00000495339.1	O60603

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68159

AN:

151920

Hom.:

15500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.498

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

GnomAD4 genome

AF:

0.448

AC:

68170

AN:

152038

Hom.:

15503

Cov.:

AF XY:

0.443

AC XY:

32950

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.383

AC:

15888

AN:

41450

American (AMR)

AF:

0.374

AC:

5709

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1481

AN:

3472

East Asian (EAS)

AF:

0.580

AC:

3000

AN:

5170

South Asian (SAS)

AF:

0.337

AC:

1625

AN:

4820

European-Finnish (FIN)

AF:

0.457

AC:

4832

AN:

10576

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34213

AN:

67964

Other (OTH)

AF:

0.496

AC:

1045

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1950

3900

5850

7800

9750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.475

Hom.:

2270

Bravo

AF:

0.443

Asia WGS

AF:

0.432

AC:

1498

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.2

(source)

DANN

Benign

0.80

PhyloP100

0.43

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