dbSNP rs1898830: TLR2:c.-162-601A>G (chr4-153687301-A-G) – 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.-162-601A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,062 control chromosomes in the GnomAD database, including 8,193 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 0.31 ( 8193 hom., cov: 32)

Consequence

TLR2
NM_001318789.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.320

Publications

103 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:

Genome browser will be placed here

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=-0.68).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 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.-162-601A>G	intron	N/A	NP_001305718.1	O60603
TLR2	NM_001318787.2		c.-372-616A>G	intron	N/A	NP_001305716.1	A0A0S2Z4S4
TLR2	NM_001318790.2		c.-162-601A>G	intron	N/A	NP_001305719.1	A0A0S2Z4S4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR2	ENST00000642700.2	MANE Select	c.-162-601A>G	intron	N/A	ENSP00000494425.1	O60603
TLR2	ENST00000260010.7	TSL:6	c.-1554-601A>G	intron	N/A	ENSP00000260010.6	O60603
TLR2	ENST00000642580.1		c.-88-616A>G	intron	N/A	ENSP00000495339.1	O60603

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46841

AN:

151942

Hom.:

8176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.297

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

GnomAD4 genome

AF:

0.308

AC:

46871

AN:

152062

Hom.:

8193

Cov.:

AF XY:

0.317

AC XY:

23584

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.136

AC:

5661

AN:

41520

American (AMR)

AF:

0.447

AC:

6825

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1364

AN:

3472

East Asian (EAS)

AF:

0.424

AC:

2191

AN:

5168

South Asian (SAS)

AF:

0.539

AC:

2602

AN:

4828

European-Finnish (FIN)

AF:

0.340

AC:

3572

AN:

10520

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.345

AC:

23439

AN:

67964

Other (OTH)

AF:

0.301

AC:

636

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1586

3173

4759

6346

7932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.332

Hom.:

4061

Bravo

AF:

0.307

Asia WGS

AF:

0.477

AC:

1650

AN:

3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.5

(source)

DANN

Benign

0.89

PhyloP100

-0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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