4-153704530-C-T

Variant names:

• chr4-153704530-C-T
• rs5743700
• NM_001318789.2:c.1623C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001318789.2(TLR2):​c.1623C>T​(p.Phe541Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 1,613,916 control chromosomes in the GnomAD database, including 2,163 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 0.036 (170 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1993 hom.)
• Consequence: TLR2 NM_001318789.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 14 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0519 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR2	NM_001318789.2	MANE Select	c.1623C>T	p.Phe541Phe	synonymous	Exon 3 of 3	NP_001305718.1	O60603
	TLR2	NM_001318787.2		c.1623C>T	p.Phe541Phe	synonymous	Exon 4 of 4	NP_001305716.1	A0A0S2Z4S4
	TLR2	NM_001318790.2		c.1623C>T	p.Phe541Phe	synonymous	Exon 3 of 3	NP_001305719.1	A0A0S2Z4S4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR2	ENST00000642700.2	MANE Select	c.1623C>T	p.Phe541Phe	synonymous	Exon 3 of 3	ENSP00000494425.1	O60603
	TLR2	ENST00000260010.7	TSL:6	c.1623C>T	p.Phe541Phe	synonymous	Exon 3 of 3	ENSP00000260010.6	O60603
	TLR2	ENST00000642580.1		c.1623C>T	p.Phe541Phe	synonymous	Exon 3 of 3	ENSP00000495339.1	O60603

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5483 AN: 152064 Hom.: 171 Cov.: 32

Gnomad AFR AF: 0.00886

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0373

GnomAD2 exomes AF: 0.0386 AC: 9675 AN: 250334 AF XY: 0.0397

Gnomad AFR exome AF: 0.00771

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0972

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0402

Gnomad NFE exome AF: 0.0547

Gnomad OTH exome AF: 0.0465

GnomAD4 exome AF: 0.0484 AC: 70759 AN: 1461734 Hom.: 1993 Cov.: 34 AF XY: 0.0480 AC XY: 34883 AN XY: 727160

African (AFR) AF: 0.00824 AC: 276 AN: 33478

American (AMR) AF: 0.0202 AC: 903 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2639 AN: 26126

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.0197 AC: 1703 AN: 86252

European-Finnish (FIN) AF: 0.0427 AC: 2282 AN: 53394

Middle Eastern (MID) AF: 0.0550 AC: 317 AN: 5766

European-Non Finnish (NFE) AF: 0.0537 AC: 59698 AN: 1111912

Other (OTH) AF: 0.0486 AC: 2934 AN: 60382

GnomAD4 genome AF: 0.0360 AC: 5480 AN: 152182 Hom.: 170 Cov.: 32 AF XY: 0.0340 AC XY: 2533 AN XY: 74400

African (AFR) AF: 0.00884 AC: 367 AN: 41524

American (AMR) AF: 0.0266 AC: 406 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4814

European-Finnish (FIN) AF: 0.0408 AC: 432 AN: 10594

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0533 AC: 3627 AN: 68012

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0494 Hom.: 330

Bravo AF: 0.0343

Asia WGS AF: 0.00953 AC: 34 AN: 3478

EpiCase AF: 0.0555

EpiControl AF: 0.0561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.7
DANN	Benign	0.51
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs5743700; hg19: chr4-154625682;