dbSNP rs352139: TLR9:c.4-44A>T (chr3-52224356-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017442.4(TLR9):c.4-44A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TLR9
NM_017442.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Publications

197 publications found

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:

ENSG00000173366 (HGNC:):

ENSG00000173366 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR9	NM_017442.4 link	c.4-44A>T		intron_variant	Intron 1 of 1	ENST00000360658.3	NP_059138.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TLR9	ENST00000360658.3 link	c.4-44A>T	intron_variant	Intron 1 of 1	1	NM_017442.4	ENSP00000353874.2
ENSG00000173366	ENST00000494383.1 link	c.463-44A>T	intron_variant	Intron 4 of 4	2		ENSP00000417517.1
ENSG00000173366	ENST00000478201.1 link	n.*56-89A>T	intron_variant	Intron 2 of 2	2		ENSP00000419980.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1312240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

649528

African (AFR)

AF:

0.00

AC:

AN:

29904

American (AMR)

AF:

0.00

AC:

AN:

34546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23898

East Asian (EAS)

AF:

0.00

AC:

AN:

35136

South Asian (SAS)

AF:

0.00

AC:

AN:

76364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3922

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1005244

Other (OTH)

AF:

0.00

AC:

AN:

54824

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

(source)

DANN

Benign

0.48

PhyloP100

-1.4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over