3-52224356-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 197 publications found

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: Benign. The variant received -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 rank	MANE	Protein	UniProt
TLR9	NM_017442.4	c.4-44A>G		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>G		intron_variant	Intron 1 of 1	1	NM_017442.4	ENSP00000353874.2
ENSG00000173366	ENST00000494383.1	c.463-44A>G		intron_variant	Intron 4 of 4	2		ENSP00000417517.1
ENSG00000173366	ENST00000478201.1	n.*56-89A>G		intron_variant	Intron 2 of 2	2		ENSP00000419980.1

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

GnomAD2 exomes AF: 0.513 AC: 74684 AN: 145474 AF XY: 0.505

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 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

African (AFR) AF: 0.590 AC: 17606 AN: 29858

American (AMR) AF: 0.545 AC: 18821 AN: 34510

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 13339 AN: 23868

East Asian (EAS) AF: 0.450 AC: 15797 AN: 35108

South Asian (SAS) AF: 0.417 AC: 31809 AN: 76282

European-Finnish (FIN) AF: 0.496 AC: 23973 AN: 48374

Middle Eastern (MID) AF: 0.521 AC: 2042 AN: 3918

European-Non Finnish (NFE) AF: 0.546 AC: 547676 AN: 1003382

Other (OTH) AF: 0.516 AC: 28265 AN: 54734

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

African (AFR) AF: 0.578 AC: 23918 AN: 41370

American (AMR) AF: 0.543 AC: 8278 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1923 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2026 AN: 5142

South Asian (SAS) AF: 0.422 AC: 2028 AN: 4810

European-Finnish (FIN) AF: 0.480 AC: 5065 AN: 10548

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37199 AN: 67884

Other (OTH) AF: 0.546 AC: 1152 AN: 2110

Alfa AF: 0.546 Hom.: 62516

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs352139; hg19: chr3-52258372; COSMIC: COSV59726450; COSMIC: COSV59726450;