rs179014

Variant names:

• chrX-12881646-A-G
• rs179014
• NM_016562.4:c.4-3866A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-12881646-A-G
• chrX-12881646-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016562.4(TLR7):​c.4-3866A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.85 (28226 hom., 24172 hem., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 5 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: PanelApp Australia, Baylor College of Medicine Research Center, ClinGen
• immunodeficiency 74, COVID-19-related, X-linked

  Inheritance: Unknown, XL Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016562.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR7	NM_016562.4	MANE Select	c.4-3866A>G		intron	N/A	NP_057646.1	B2R9N9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR7	ENST00000380659.4	TSL:1 MANE Select	c.4-3866A>G		intron	N/A	ENSP00000370034.3	Q9NYK1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 89768 AN: 105695 Hom.: 28228 Cov.: 19

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.871

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.871

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.849 AC: 89798 AN: 105718 Hom.: 28226 Cov.: 19 AF XY: 0.846 AC XY: 24172 AN XY: 28564

African (AFR) AF: 0.963 AC: 27944 AN: 29010

American (AMR) AF: 0.893 AC: 8658 AN: 9698

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2024 AN: 2579

East Asian (EAS) AF: 0.999 AC: 3365 AN: 3369

South Asian (SAS) AF: 0.929 AC: 2183 AN: 2351

European-Finnish (FIN) AF: 0.769 AC: 3696 AN: 4808

Middle Eastern (MID) AF: 0.866 AC: 181 AN: 209

European-Non Finnish (NFE) AF: 0.777 AC: 40147 AN: 51638

Other (OTH) AF: 0.873 AC: 1237 AN: 1417

Alfa AF: 0.820 Hom.: 7570

Bravo AF: 0.869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		0.033
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: rs179014; hg19: chrX-12899765;