XM_047416111.1:c.*1241T>G

Variant names:

• chr4-153706503-T-G
• rs7656411
• XM_047416111.1:c.*1241T>G

Variant summary

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

The XM_047416111.1(TLR2):​c.*1241T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,098 control chromosomes in the GnomAD database, including 10,724 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 0.34 (10724 hom., cov: 32)
• Consequence: TLR2 XM_047416111.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 80 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642700.2. 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.*1241T>G		downstream_gene	N/A	NP_001305718.1
	TLR2	NM_001318787.2		c.*1241T>G		downstream_gene	N/A	NP_001305716.1
	TLR2	NM_001318790.2		c.*1241T>G		downstream_gene	N/A	NP_001305719.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR2	ENST00000642700.2	MANE Select	c.*1241T>G		downstream_gene	N/A	ENSP00000494425.1
	TLR2	ENST00000643501.2		c.*1241T>G		downstream_gene	N/A	ENSP00000496208.2
	TLR2	ENST00000646219.2		c.*1241T>G		downstream_gene	N/A	ENSP00000496676.2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52226 AN: 151980 Hom.: 10698 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.344 AC: 52299 AN: 152098 Hom.: 10724 Cov.: 32 AF XY: 0.339 AC XY: 25215 AN XY: 74362

African (AFR) AF: 0.567 AC: 23511 AN: 41458

American (AMR) AF: 0.302 AC: 4620 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1046 AN: 3470

East Asian (EAS) AF: 0.486 AC: 2509 AN: 5166

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1453 AN: 10592

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16828 AN: 67992

Other (OTH) AF: 0.364 AC: 770 AN: 2114

Alfa AF: 0.283 Hom.: 23241

Bravo AF: 0.367

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs7656411; hg19: chr4-154627655;