X-12871738-A-G

Variant names:

• chrX-12871738-A-G
• rs179020
• NM_016562.4:c.3+4157A>G

Variant summary

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

The NM_016562.4(TLR7):​c.3+4157A>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 0.80 (25029 hom., 25880 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 6 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=-0.98).

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.3+4157A>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.3+4157A>G		intron	N/A	ENSP00000370034.3	Q9NYK1
	TLR7	ENST00000484204.1	TSL:3	n.103+4157A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.799 AC: 88080 AN: 110203 Hom.: 25039 Cov.: 22

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.816

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: 0.799 AC: 88127 AN: 110256 Hom.: 25029 Cov.: 22 AF XY: 0.797 AC XY: 25880 AN XY: 32480

African (AFR) AF: 0.868 AC: 26289 AN: 30291

American (AMR) AF: 0.840 AC: 8717 AN: 10383

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 1982 AN: 2625

East Asian (EAS) AF: 0.747 AC: 2601 AN: 3480

South Asian (SAS) AF: 0.728 AC: 1866 AN: 2564

European-Finnish (FIN) AF: 0.768 AC: 4431 AN: 5767

Middle Eastern (MID) AF: 0.843 AC: 182 AN: 216

European-Non Finnish (NFE) AF: 0.767 AC: 40459 AN: 52770

Other (OTH) AF: 0.814 AC: 1214 AN: 1492

Alfa AF: 0.775 Hom.: 16270

Bravo AF: 0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.1
DANN	Benign	0.42
PhyloP100		0.63
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: rs179020; hg19: chrX-12889857;