chrX-12883443-G-A

Variant names:

• chrX-12883443-G-A
• rs179012
• NM_016562.4:c.4-2069G>A

Variant summary

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

The NM_016562.4(TLR7):​c.4-2069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 110,451 control chromosomes in the GnomAD database, including 8,191 homozygotes. There are 12,999 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 0.41 (8191 hom., 12999 hem., cov: 22)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 29 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.4-2069G>A		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.4-2069G>A		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 45024 AN: 110397 Hom.: 8187 Cov.: 22

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0803

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.408 AC: 45062 AN: 110451 Hom.: 8191 Cov.: 22 AF XY: 0.397 AC XY: 12999 AN XY: 32709

African (AFR) AF: 0.713 AC: 21623 AN: 30323

American (AMR) AF: 0.354 AC: 3675 AN: 10373

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 546 AN: 2633

East Asian (EAS) AF: 0.0803 AC: 284 AN: 3538

South Asian (SAS) AF: 0.109 AC: 287 AN: 2642

European-Finnish (FIN) AF: 0.372 AC: 2156 AN: 5789

Middle Eastern (MID) AF: 0.260 AC: 56 AN: 215

European-Non Finnish (NFE) AF: 0.298 AC: 15731 AN: 52767

Other (OTH) AF: 0.354 AC: 530 AN: 1496

Alfa AF: 0.335 Hom.: 30148

Bravo AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.75
PhyloP100		0.10
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: rs179012; hg19: chrX-12901562;