rs864058

Variant names:

• chrX-12887911-G-A
• rs864058
• NM_016562.4:c.2403G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_016562.4(TLR7):​c.2403G>A​(p.Thr801Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 1,209,370 control chromosomes in the GnomAD database, including 3,807 homozygotes. There are 33,262 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (838 hom., 3631 hem., cov: 23)
  • Exomes 𝑓: 0.082 (2969 hom. 29631 hem.)
• Consequence: TLR7 NM_016562.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65
• Publications: 32 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-12887911-G-A is Benign according to our data. Variant chrX-12887911-G-A is described in ClinVar as Benign. ClinVar VariationId is 2127820.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR7	NM_016562.4	MANE Select	c.2403G>A	p.Thr801Thr	synonymous	Exon 3 of 3	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.2403G>A	p.Thr801Thr	synonymous	Exon 3 of 3	ENSP00000370034.3	Q9NYK1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 13528 AN: 111146 Hom.: 838 Cov.: 23

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00869

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.0796 AC: 14579 AN: 183039 AF XY: 0.0773

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.0484

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.00404

Gnomad FIN exome AF: 0.0483

Gnomad NFE exome AF: 0.0862

Gnomad OTH exome AF: 0.0893

GnomAD4 exome AF: 0.0821 AC: 90186 AN: 1098171 Hom.: 2969 Cov.: 33 AF XY: 0.0815 AC XY: 29631 AN XY: 363539

African (AFR) AF: 0.245 AC: 6459 AN: 26402

American (AMR) AF: 0.0541 AC: 1904 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.0990 AC: 1919 AN: 19385

East Asian (EAS) AF: 0.0162 AC: 488 AN: 30206

South Asian (SAS) AF: 0.0604 AC: 3273 AN: 54145

European-Finnish (FIN) AF: 0.0502 AC: 2035 AN: 40525

Middle Eastern (MID) AF: 0.140 AC: 581 AN: 4137

European-Non Finnish (NFE) AF: 0.0823 AC: 69265 AN: 842076

Other (OTH) AF: 0.0925 AC: 4262 AN: 46092

GnomAD4 genome AF: 0.122 AC: 13533 AN: 111199 Hom.: 838 Cov.: 23 AF XY: 0.109 AC XY: 3631 AN XY: 33443

African (AFR) AF: 0.231 AC: 7025 AN: 30462

American (AMR) AF: 0.0972 AC: 1025 AN: 10541

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 275 AN: 2633

East Asian (EAS) AF: 0.00872 AC: 31 AN: 3555

South Asian (SAS) AF: 0.0539 AC: 142 AN: 2633

European-Finnish (FIN) AF: 0.0395 AC: 236 AN: 5976

Middle Eastern (MID) AF: 0.136 AC: 29 AN: 214

European-Non Finnish (NFE) AF: 0.0843 AC: 4468 AN: 53006

Other (OTH) AF: 0.122 AC: 183 AN: 1501

Alfa AF: 0.105 Hom.: 7828

Bravo AF: 0.133

EpiCase AF: 0.0971

EpiControl AF: 0.0990

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.073
DANN	Benign	0.58
PhyloP100		-1.7
Mutation Taster		=98/2	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: rs864058; hg19: chrX-12906030; COSMIC: COSV66125729;