rs5743740

Variant names:

• chrX-12873841-A-G
• rs5743740
• NM_016562.4:c.3+6260A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-12873841-A-G
• chrX-12873841-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.3+6260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 111,594 control chromosomes in the GnomAD database, including 1,045 homozygotes. There are 4,169 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 0.13 (1045 hom., 4169 hem., cov: 23)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• 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: 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.3+6260A>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.3+6260A>G		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3
TLR7	ENST00000484204.1	n.104-3603A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 14257 AN: 111547 Hom.: 1043 Cov.: 23

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.0702

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0586

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0994

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

GnomAD4 genome AF: 0.128 AC: 14291 AN: 111594 Hom.: 1045 Cov.: 23 AF XY: 0.123 AC XY: 4169 AN XY: 33846

African (AFR) AF: 0.278 AC: 8477 AN: 30539

American (AMR) AF: 0.0989 AC: 1045 AN: 10561

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 186 AN: 2650

East Asian (EAS) AF: 0.129 AC: 463 AN: 3590

South Asian (SAS) AF: 0.111 AC: 297 AN: 2681

European-Finnish (FIN) AF: 0.0686 AC: 412 AN: 6006

Middle Eastern (MID) AF: 0.0596 AC: 13 AN: 218

European-Non Finnish (NFE) AF: 0.0611 AC: 3247 AN: 53134

Other (OTH) AF: 0.0982 AC: 150 AN: 1528

Alfa AF: 0.0918 Hom.: 4506

Bravo AF: 0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		0.41
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: rs5743740; hg19: chrX-12891960;