rs5743698

chr4-153703546-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001318789.2(TLR2):c.639G>C(p.Leu213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,614,100 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (5 hom.)
• Consequence: TLR2 NM_001318789.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.421

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-153703546-G-C is Benign according to our data. Variant chr4-153703546-G-C is described in ClinVar as [Benign]. Clinvar id is 740672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.421 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR2	NM_001318789.2	c.639G>C	p.Leu213=	synonymous_variant	3/3	ENST00000642700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR2	ENST00000642700.2	c.639G>C	p.Leu213=	synonymous_variant	3/3		NM_001318789.2	P1

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 208 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00237

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00129 AC: 323 AN: 251108 Hom.: 1 AF XY: 0.00124 AC XY: 169 AN XY: 135750

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000955

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000833

Gnomad NFE exome AF: 0.00230

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00139 AC: 2032 AN: 1461762 Hom.: 5 Cov.: 35 AF XY: 0.00142 AC XY: 1035 AN XY: 727176

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000712

Gnomad4 NFE exome AF: 0.00167

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00123 AC XY: 92 AN XY: 74496

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00237

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00179 Hom.: 0

Bravo AF: 0.00129

EpiCase AF: 0.00207

EpiControl AF: 0.00154

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.49
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743698; hg19: chr4-154624698;