rs5743688

Variant names:

• chr4-153686216-G-A
• rs5743688
• NM_001318789.2:c.-162-1686G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-153686216-G-A
• chr4-153686216-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 2 publications found

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR2	NM_001318789.2	c.-162-1686G>A		intron_variant	Intron 1 of 2	ENST00000642700.2	NP_001305718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR2	ENST00000642700.2	c.-162-1686G>A		intron_variant	Intron 1 of 2		NM_001318789.2	ENSP00000494425.1

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12466 AN: 152034 Hom.: 689 Cov.: 32

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.: 32 AF XY: 0.0851 AC XY: 6327 AN XY: 74362

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: 17 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: 25 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7107 AN: 67984

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.0334 Hom.: 38

Bravo AF: 0.0724

Asia WGS AF: 0.0430 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.48
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs5743688; hg19: chr4-154607368;