rs179011

Variant names:

• chrX-12883841-G-T
• rs179011
• NM_016562.4:c.4-1671G>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.4-1671G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 110,077 control chromosomes in the GnomAD database, including 3,154 homozygotes. There are 8,048 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 0.26 (3154 hom., 8048 hem., cov: 22)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.4-1671G>T		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.4-1671G>T		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 28669 AN: 110021 Hom.: 3153 Cov.: 22

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.261 AC: 28685 AN: 110077 Hom.: 3154 Cov.: 22 AF XY: 0.249 AC XY: 8048 AN XY: 32377

African (AFR) AF: 0.401 AC: 12082 AN: 30105

American (AMR) AF: 0.246 AC: 2564 AN: 10436

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 431 AN: 2618

East Asian (EAS) AF: 0.0121 AC: 43 AN: 3550

South Asian (SAS) AF: 0.0555 AC: 143 AN: 2578

European-Finnish (FIN) AF: 0.271 AC: 1557 AN: 5745

Middle Eastern (MID) AF: 0.172 AC: 36 AN: 209

European-Non Finnish (NFE) AF: 0.215 AC: 11333 AN: 52663

Other (OTH) AF: 0.234 AC: 351 AN: 1499

Alfa AF: 0.251 Hom.: 2665

Bravo AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.34
PhyloP100		0.0040
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: rs179011; hg19: chrX-12901960;