Variant 3-52222681-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000360658.3(TLR9):c.1635G>A(p.Pro545=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,612,878 control chromosomes in the GnomAD database, including 214,754 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 0.47 ( 17292 hom., cov: 34)

Exomes 𝑓: 0.52 ( 197462 hom. )

Consequence

TLR9
ENST00000360658.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.75

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]

TLR9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-5.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR9	NM_017442.4 linkuse as main transcript	c.1635G>A	p.Pro545=	synonymous_variant	2/2	ENST00000360658.3	NP_059138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR9	ENST00000360658.3 linkuse as main transcript	c.1635G>A	p.Pro545=	synonymous_variant	2/2	1	NM_017442.4	ENSP00000353874	P1	Q9NR96-1

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70882

AN:

152002

Hom.:

17291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.490

GnomAD3 exomes

AF:

0.495

AC:

123979

AN:

250650

Hom.:

31417

AF XY:

0.495

AC XY:

67057

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.370

Gnomad SAS exome

AF:

0.417

Gnomad FIN exome

AF:

0.491

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.510

GnomAD4 exome

AF:

0.518

AC:

756250

AN:

1460758

Hom.:

197462

Cov.:

AF XY:

0.515

AC XY:

374401

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.337

Gnomad4 AMR exome

AF:

0.522

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.494

Gnomad4 NFE exome

AF:

0.536

Gnomad4 OTH exome

AF:

0.490

GnomAD4 genome

AF:

0.466

AC:

70899

AN:

152120

Hom.:

17292

Cov.:

AF XY:

0.462

AC XY:

34390

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.508

Gnomad4 ASJ

AF:

0.550

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.419

Gnomad4 FIN

AF:

0.477

Gnomad4 NFE

AF:

0.539

Gnomad4 OTH

AF:

0.492

Alfa

AF:

0.520

Hom.:

20643

Bravo

AF:

0.464

Asia WGS

AF:

0.411

AC:

1431

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.063

DANN

Benign

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over