rs352139

Variant names:

• chr3-52224356-T-A
• rs352139
• NM_017442.4:c.4-44A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-52224356-T-A
• chr3-52224356-T-C
• chr3-52224356-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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]

ENSG00000173366 (HGNC:):

ACMG classification

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	c.4-44A>T		intron_variant	Intron 1 of 1	ENST00000360658.3	NP_059138.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1312240 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 649528

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 29904

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 34546

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 23898

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35136

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 76364

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 48402

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 1005244

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 54824

GnomAD4 genome Cov.: 31

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
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

Other links and lift over

dbSNP: rs352139; hg19: chr3-52258372;