3-52224356-T-C

Position:

• chr3-52224356-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017442.4(TLR9):​c.4-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,461,814 control chromosomes in the GnomAD database, including 210,038 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 0.54 (22536 hom., cov: 31)
  • Exomes 𝑓: 0.53 (187502 hom.)
• 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR9	NM_017442.4	c.4-44A>G		intron_variant		ENST00000360658.3	NP_059138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR9	ENST00000360658.3	c.4-44A>G		intron_variant		1	NM_017442.4	ENSP00000353874	P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82235 AN: 151662 Hom.: 22514 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.544

GnomAD3 exomes AF: 0.513 AC: 74684 AN: 145474 Hom.: 19536 AF XY: 0.505 AC XY: 38719 AN XY: 76598

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.546

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.371

Gnomad SAS exome AF: 0.422

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.516

GnomAD4 exome AF: 0.534 AC: 699328 AN: 1310034 Hom.: 187502 Cov.: 20 AF XY: 0.530 AC XY: 343649 AN XY: 648494

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.559

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.546

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.542 AC: 82309 AN: 151780 Hom.: 22536 Cov.: 31 AF XY: 0.537 AC XY: 39806 AN XY: 74182

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.546

Alfa AF: 0.541 Hom.: 25263

Bravo AF: 0.550

Asia WGS AF: 0.444 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.32

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; COSMIC: COSV59726450; COSMIC: COSV59726450;