rs1898830

chr4-153687301-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR2	NM_001318789.2	c.-162-601A>G		intron_variant		ENST00000642700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR2	ENST00000642700.2	c.-162-601A>G		intron_variant			NM_001318789.2	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46841 AN: 151942 Hom.: 8176 Cov.: 32

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.: 32 AF XY: 0.317 AC XY: 23584 AN XY: 74348

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.301

Alfa AF: 0.335 Hom.: 3449

Bravo AF: 0.307

Asia WGS AF: 0.477 AC: 1650 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	4.5
Dann	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1898830; hg19: chr4-154608453;