4-153684593-C-T

Position:

• chr4-153684593-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR2	NM_001318789.2	c.-163+233C>T		intron_variant		ENST00000642700.2	NP_001305718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR2	ENST00000642700.2	c.-163+233C>T		intron_variant			NM_001318789.2	ENSP00000494425	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39724 AN: 152080 Hom.: 5777 Cov.: 33

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.: 33 AF XY: 0.257 AC XY: 19157 AN XY: 74426

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.289

Alfa AF: 0.323 Hom.: 13873

Bravo AF: 0.249

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7696323; hg19: chr4-154605745;