rs179017

Variant names:

• chrX-12875674-A-C
• rs179017
• NM_016562.4:c.3+8093A>C

Variant summary

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

The NM_016562.4(TLR7):​c.3+8093A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 111,354 control chromosomes in the GnomAD database, including 219 homozygotes. There are 1,899 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 0.058 (219 hom., 1899 hem., cov: 23)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.3+8093A>C		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.3+8093A>C		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3
TLR7	ENST00000484204.1	n.104-1770A>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 6495 AN: 111300 Hom.: 219 Cov.: 23

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0643

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.0146

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0295

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0583 AC: 6495 AN: 111354 Hom.: 219 Cov.: 23 AF XY: 0.0566 AC XY: 1899 AN XY: 33546

African (AFR) AF: 0.0105 AC: 323 AN: 30645

American (AMR) AF: 0.0325 AC: 343 AN: 10543

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 86 AN: 2650

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3542

South Asian (SAS) AF: 0.0151 AC: 40 AN: 2657

European-Finnish (FIN) AF: 0.123 AC: 730 AN: 5925

Middle Eastern (MID) AF: 0.0324 AC: 7 AN: 216

European-Non Finnish (NFE) AF: 0.0914 AC: 4843 AN: 52982

Other (OTH) AF: 0.0517 AC: 78 AN: 1510

Alfa AF: 0.0861 Hom.: 497

Bravo AF: 0.0489

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.69
PhyloP100		0.35
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: rs179017; hg19: chrX-12893793;