rs4696480

chr4-153685974-T-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR2	NM_001318789.2	c.-163+1614T>A		intron_variant		ENST00000642700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR2	ENST00000642700.2	c.-163+1614T>A		intron_variant			NM_001318789.2	P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68159 AN: 151920 Hom.: 15500 Cov.: 32

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.: 32 AF XY: 0.443 AC XY: 32950 AN XY: 74306

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.496

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	8.2
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4696480; hg19: chr4-154607126;