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4-153703021-C-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001318789.2(TLR2):c.114C>A(p.Gly38=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.773
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-153703021-C-A is Benign according to our data. Variant chr4-153703021-C-A is described in ClinVar as [Benign]. Clinvar id is 786049.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.773 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLR2NM_001318789.2 linkuse as main transcriptc.114C>A p.Gly38= synonymous_variant 3/3 ENST00000642700.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR2ENST00000642700.2 linkuse as main transcriptc.114C>A p.Gly38= synonymous_variant 3/3 NM_001318789.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00326
AC:
496
AN:
151972
Hom.:
3
Cov.:
31
show subpopulations
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
GnomAD3 exomes
AF:
0.00162
AC:
407
AN:
251432
Hom.:
0
AF XY:
0.00129
AC XY:
175
AN XY:
135896
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.0106
Gnomad4 AMR exome
AF:
0.00440
Gnomad4 ASJ exome
AF:
0.00130
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000538
Gnomad4 OTH exome
AF:
0.00171
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00327
AC:
497
AN:
152090
Hom.:
3
Cov.:
31
AF XY:
0.00340
AC XY:
253
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00983
Gnomad4 AMR
AF:
0.00255
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000544
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00153
Hom.:
1
Bravo
AF:
0.00366
EpiCase
AF:
0.000981
EpiControl
AF:
0.000889

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
3.8
Dann
Benign
0.35

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5743697; hg19: chr4-154624173; API