chr4-153698103-T-C

Variant names:

• chr4-153698103-T-C
• rs4696483
• NM_001318789.2:c.-16-4789T>C

Variant summary

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

The NM_001318789.2(TLR2):​c.-16-4789T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,048 control chromosomes in the GnomAD database, including 48,883 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 0.79 (48883 hom., cov: 32)
• Consequence: TLR2 NM_001318789.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 24 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR2	NM_001318789.2	MANE Select	c.-16-4789T>C		intron	N/A	NP_001305718.1
	TLR2	NM_001318787.2		c.-300-4124T>C		intron	N/A	NP_001305716.1
	TLR2	NM_001318790.2		c.-16-4789T>C		intron	N/A	NP_001305719.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR2	ENST00000642700.2	MANE Select	c.-16-4789T>C		intron	N/A	ENSP00000494425.1
	TLR2	ENST00000260010.7	TSL:6	c.-1408-3397T>C		intron	N/A	ENSP00000260010.6
	TLR2	ENST00000642580.1		c.-16-4789T>C		intron	N/A	ENSP00000495339.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120292 AN: 151930 Hom.: 48866 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.792 AC: 120351 AN: 152048 Hom.: 48883 Cov.: 32 AF XY: 0.794 AC XY: 59001 AN XY: 74336

African (AFR) AF: 0.588 AC: 24360 AN: 41446

American (AMR) AF: 0.836 AC: 12760 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2888 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5163 AN: 5182

South Asian (SAS) AF: 0.891 AC: 4298 AN: 4824

European-Finnish (FIN) AF: 0.824 AC: 8726 AN: 10588

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59422 AN: 67962

Other (OTH) AF: 0.827 AC: 1740 AN: 2104

Alfa AF: 0.840 Hom.: 15757

Bravo AF: 0.786

Asia WGS AF: 0.917 AC: 3185 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.19
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs4696483; hg19: chr4-154619255;