chr4-153703021-C-A

Variant names:

• chr4-153703021-C-A
• rs5743697
• NM_001318789.2:c.114C>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001318789.2(TLR2):​c.114C>A​(p.Gly38Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,970 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00090 (4 hom.)
• Consequence: TLR2 NM_001318789.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.773
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 4-153703021-C-A is Benign according to our data. Variant chr4-153703021-C-A is described in ClinVar as Benign. ClinVar VariationId is 786049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.773 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

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.114C>A	p.Gly38Gly	synonymous	Exon 3 of 3	NP_001305718.1	O60603
	TLR2	NM_001318787.2		c.114C>A	p.Gly38Gly	synonymous	Exon 4 of 4	NP_001305716.1	A0A0S2Z4S4
	TLR2	NM_001318790.2		c.114C>A	p.Gly38Gly	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.114C>A	p.Gly38Gly	synonymous	Exon 3 of 3	ENSP00000494425.1	O60603
	TLR2	ENST00000260010.7	TSL:6	c.114C>A	p.Gly38Gly	synonymous	Exon 3 of 3	ENSP00000260010.6	O60603
	TLR2	ENST00000642580.1		c.114C>A	p.Gly38Gly	synonymous	Exon 3 of 3	ENSP00000495339.1	O60603

Frequencies

GnomAD3 genomes AF: 0.00326 AC: 496 AN: 151972 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00986

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00162 AC: 407 AN: 251432 AF XY: 0.00129

Gnomad AFR exome AF: 0.00910

Gnomad AMR exome AF: 0.00466

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000607

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.000897 AC: 1311 AN: 1461880 Hom.: 4 Cov.: 32 AF XY: 0.000807 AC XY: 587 AN XY: 727242

African (AFR) AF: 0.0106 AC: 354 AN: 33480

American (AMR) AF: 0.00440 AC: 197 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000538 AC: 598 AN: 1112004

Other (OTH) AF: 0.00171 AC: 103 AN: 60394

GnomAD4 genome AF: 0.00327 AC: 497 AN: 152090 Hom.: 3 Cov.: 31 AF XY: 0.00340 AC XY: 253 AN XY: 74344

African (AFR) AF: 0.00983 AC: 408 AN: 41486

American (AMR) AF: 0.00255 AC: 39 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68000

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00153 Hom.: 1

Bravo AF: 0.00366

EpiCase AF: 0.000981

EpiControl AF: 0.000889

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.8
DANN	Benign	0.35
PhyloP100		0.77
PromoterAI		-0.017	Neutral
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs5743697; hg19: chr4-154624173;