rs179009

Variant names:

• chrX-12885361-A-G
• rs179009
• NM_016562.4:c.4-151A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-12885361-A-G
• chrX-12885361-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016562.4(TLR7):​c.4-151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 497,934 control chromosomes in the GnomAD database, including 8,349 homozygotes. There are 31,188 hemizygotes in GnomAD. 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 0.21 (1788 hom., 7032 hem., cov: 23)
  • Exomes 𝑓: 0.21 (6561 hom. 24156 hem.)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 37 publications found

Genes affected

TLR7 (HGNC:15631): (toll like receptor 7) 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. The human TLR family comprises 11 members. 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. For the recognition of structural components in foreign microorganisms, the various TLRs exhibit different patterns of expression as well; in this way for example, TLR-3, -7, and -8 are essential in the recognition of single-stranded RNA viruses. TLR7 senses single-stranded RNA oligonucleotides containing guanosine- and uridine-rich sequences from RNA viruses, a recognition occuring in the endosomes of plasmacytoid dendritic cells and B cells. This gene is predominantly expressed in lung, placenta, and spleen, and is phylogenetically related and lies in close proximity to another family member, TLR8, on chromosome X. [provided by RefSeq, Aug 2020]

TLR7 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus 17

  Inheritance: XL Classification: MODERATE Submitted by: Baylor College of Medicine Research Center
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency 74, COVID-19-related, X-linked

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.4-151A>G		intron_variant	Intron 2 of 2	ENST00000380659.4	NP_057646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4	c.4-151A>G		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 23453 AN: 111694 Hom.: 1785 Cov.: 23

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.210 AC: 81270 AN: 386183 Hom.: 6561 AF XY: 0.205 AC XY: 24156 AN XY: 117583

African (AFR) AF: 0.162 AC: 1837 AN: 11365

American (AMR) AF: 0.320 AC: 5990 AN: 18716

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 1820 AN: 10274

East Asian (EAS) AF: 0.140 AC: 3610 AN: 25840

South Asian (SAS) AF: 0.0801 AC: 1782 AN: 22237

European-Finnish (FIN) AF: 0.274 AC: 9030 AN: 32999

Middle Eastern (MID) AF: 0.184 AC: 258 AN: 1399

European-Non Finnish (NFE) AF: 0.217 AC: 52546 AN: 241896

Other (OTH) AF: 0.205 AC: 4397 AN: 21457

GnomAD4 genome AF: 0.210 AC: 23474 AN: 111751 Hom.: 1788 Cov.: 23 AF XY: 0.207 AC XY: 7032 AN XY: 33949

African (AFR) AF: 0.164 AC: 5076 AN: 30877

American (AMR) AF: 0.310 AC: 3261 AN: 10533

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 468 AN: 2649

East Asian (EAS) AF: 0.163 AC: 580 AN: 3568

South Asian (SAS) AF: 0.0854 AC: 231 AN: 2706

European-Finnish (FIN) AF: 0.279 AC: 1652 AN: 5929

Middle Eastern (MID) AF: 0.155 AC: 33 AN: 213

European-Non Finnish (NFE) AF: 0.220 AC: 11687 AN: 53075

Other (OTH) AF: 0.223 AC: 339 AN: 1522

Alfa AF: 0.186 Hom.: 3670

Bravo AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.050
DANN	Benign	0.74
PhyloP100		-1.5
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: rs179009; hg19: chrX-12903480;