rs1634319

Variant names:

• chrX-12884916-T-C
• rs1634319
• NM_016562.4:c.4-596T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016562.4(TLR7):​c.4-596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 112,716 control chromosomes in the GnomAD database, including 1,109 homozygotes. There are 4,138 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 (1109 hom., 4138 hem., cov: 24)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.4-596T>C		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.4-596T>C		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 14624 AN: 112661 Hom.: 1106 Cov.: 24

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.0376

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.130 AC: 14633 AN: 112716 Hom.: 1109 Cov.: 24 AF XY: 0.119 AC XY: 4138 AN XY: 34902

African (AFR) AF: 0.282 AC: 8715 AN: 30953

American (AMR) AF: 0.0940 AC: 1006 AN: 10702

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 459 AN: 2652

East Asian (EAS) AF: 0.0549 AC: 198 AN: 3608

South Asian (SAS) AF: 0.0374 AC: 104 AN: 2781

European-Finnish (FIN) AF: 0.0210 AC: 131 AN: 6242

Middle Eastern (MID) AF: 0.165 AC: 36 AN: 218

European-Non Finnish (NFE) AF: 0.0694 AC: 3699 AN: 53333

Other (OTH) AF: 0.125 AC: 193 AN: 1544

Alfa AF: 0.119 Hom.: 635

Bravo AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.83
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: rs1634319; hg19: chrX-12903035;