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GeneBe

3-52221223-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_017442.4(TLR9):c.3093C>T(p.Ala1031=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,511,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

TLR9
NM_017442.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.73
Variant links:
Genes affected
TLR9 (HGNC:15633): (toll like receptor 9) 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. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. Studies in mice and human indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-52221223-G-A is Benign according to our data. Variant chr3-52221223-G-A is described in ClinVar as [Benign]. Clinvar id is 713902.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=-2.72 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLR9NM_017442.4 linkuse as main transcriptc.3093C>T p.Ala1031= synonymous_variant 2/2 ENST00000360658.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR9ENST00000360658.3 linkuse as main transcriptc.3093C>T p.Ala1031= synonymous_variant 2/21 NM_017442.4 P1Q9NR96-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000348
AC:
53
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000531
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00443
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000495
AC:
87
AN:
175818
Hom.:
0
AF XY:
0.000455
AC XY:
42
AN XY:
92352
show subpopulations
Gnomad AFR exome
AF:
0.000457
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00440
Gnomad SAS exome
AF:
0.000210
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000697
Gnomad OTH exome
AF:
0.000753
GnomAD4 exome
AF:
0.000147
AC:
200
AN:
1358740
Hom.:
0
Cov.:
30
AF XY:
0.000129
AC XY:
86
AN XY:
664252
show subpopulations
Gnomad4 AFR exome
AF:
0.000233
Gnomad4 AMR exome
AF:
0.0000353
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00219
Gnomad4 SAS exome
AF:
0.000186
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000744
Gnomad4 OTH exome
AF:
0.000287
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000348
AC:
53
AN:
152302
Hom.:
0
Cov.:
33
AF XY:
0.000349
AC XY:
26
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000529
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00444
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000185
Hom.:
0
Bravo
AF:
0.000400
Asia WGS
AF:
0.00693
AC:
24
AN:
3478

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 testingInvitaeJul 27, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
0.12
Dann
Benign
0.48

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: rs144301361; hg19: chr3-52255239; API