rs11938228

Variant names:

• chr4-153700794-C-A
• rs11938228
• NM_001318789.2:c.-16-2098C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-153700794-C-A
• chr4-153700794-C-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.-16-2098C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,944 control chromosomes in the GnomAD database, including 8,943 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 0.32 (8943 hom., cov: 32)
• Consequence: TLR2 NM_001318789.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 71 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 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.-16-2098C>A		intron	N/A	NP_001305718.1
	TLR2	NM_001318787.2		c.-300-1433C>A		intron	N/A	NP_001305716.1
	TLR2	NM_001318790.2		c.-16-2098C>A		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.-16-2098C>A		intron	N/A	ENSP00000494425.1
	TLR2	ENST00000260010.7	TSL:6	c.-1408-706C>A		intron	N/A	ENSP00000260010.6
	TLR2	ENST00000642580.1		c.-16-2098C>A		intron	N/A	ENSP00000495339.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49334 AN: 151826 Hom.: 8927 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.325 AC: 49370 AN: 151944 Hom.: 8943 Cov.: 32 AF XY: 0.333 AC XY: 24748 AN XY: 74278

African (AFR) AF: 0.157 AC: 6506 AN: 41446

American (AMR) AF: 0.454 AC: 6933 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1382 AN: 3462

East Asian (EAS) AF: 0.410 AC: 2122 AN: 5172

South Asian (SAS) AF: 0.546 AC: 2632 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3835 AN: 10530

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24679 AN: 67918

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.348 Hom.: 19360

Bravo AF: 0.321

Asia WGS AF: 0.475 AC: 1648 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.68
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs11938228; hg19: chr4-154621946;