rs5743733

Variant names:

• chrX-12871589-C-G
• rs5743733
• NM_016562.4:c.3+4008C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-12871589-C-G
• chrX-12871589-C-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.3+4008C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 111,900 control chromosomes in the GnomAD database, including 447 homozygotes. There are 3,139 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 0.097 (447 hom., 3139 hem., cov: 23)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR7	NM_016562.4	MANE Select	c.3+4008C>G		intron	N/A	NP_057646.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR7	ENST00000380659.4	TSL:1 MANE Select	c.3+4008C>G		intron	N/A	ENSP00000370034.3
	TLR7	ENST00000484204.1	TSL:3	n.103+4008C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 10910 AN: 111847 Hom.: 449 Cov.: 23

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0975 AC: 10906 AN: 111900 Hom.: 447 Cov.: 23 AF XY: 0.0921 AC XY: 3139 AN XY: 34078

African (AFR) AF: 0.120 AC: 3700 AN: 30796

American (AMR) AF: 0.0905 AC: 957 AN: 10569

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 345 AN: 2647

East Asian (EAS) AF: 0.0855 AC: 306 AN: 3577

South Asian (SAS) AF: 0.179 AC: 475 AN: 2659

European-Finnish (FIN) AF: 0.0450 AC: 275 AN: 6108

Middle Eastern (MID) AF: 0.186 AC: 40 AN: 215

European-Non Finnish (NFE) AF: 0.0848 AC: 4505 AN: 53136

Other (OTH) AF: 0.112 AC: 169 AN: 1510

Alfa AF: 0.0239 Hom.: 118

Bravo AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.73
PhyloP100		-0.11
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: rs5743733; hg19: chrX-12889708;