rs1634323

Variant names:

• chrX-12870008-A-G
• rs1634323
• NM_016562.4:c.3+2427A>G

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+2427A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 109,793 control chromosomes in the GnomAD database, including 515 homozygotes. There are 3,336 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 0.11 (515 hom., 3336 hem., cov: 21)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.3+2427A>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+2427A>G		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3
TLR7	ENST00000484204.1	n.103+2427A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 12014 AN: 109738 Hom.: 516 Cov.: 21

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.109 AC: 12014 AN: 109793 Hom.: 515 Cov.: 21 AF XY: 0.104 AC XY: 3336 AN XY: 32073

African (AFR) AF: 0.140 AC: 4210 AN: 30143

American (AMR) AF: 0.0737 AC: 743 AN: 10085

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 534 AN: 2619

East Asian (EAS) AF: 0.0510 AC: 181 AN: 3550

South Asian (SAS) AF: 0.0562 AC: 145 AN: 2578

European-Finnish (FIN) AF: 0.122 AC: 692 AN: 5687

Middle Eastern (MID) AF: 0.126 AC: 27 AN: 215

European-Non Finnish (NFE) AF: 0.0998 AC: 5262 AN: 52751

Other (OTH) AF: 0.112 AC: 166 AN: 1484

Alfa AF: 0.115 Hom.: 1962

Bravo AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.46
PhyloP100		-1.6
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: rs1634323; hg19: chrX-12888127;