chrX-12876323-G-C

Variant names:

• chrX-12876323-G-C
• rs179016
• NM_016562.4:c.3+8742G>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.3+8742G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 110,444 control chromosomes in the GnomAD database, including 10,916 homozygotes. There are 15,669 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 0.49 (10916 hom., 15669 hem., cov: 22)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 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.3+8742G>C		intron	N/A	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.3+8742G>C		intron	N/A	ENSP00000370034.3	Q9NYK1
	TLR7	ENST00000484204.1	TSL:3	n.104-1121G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.488 AC: 53830 AN: 110397 Hom.: 10911 Cov.: 22

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.488 AC: 53883 AN: 110444 Hom.: 10916 Cov.: 22 AF XY: 0.479 AC XY: 15669 AN XY: 32720

African (AFR) AF: 0.790 AC: 23929 AN: 30286

American (AMR) AF: 0.412 AC: 4261 AN: 10348

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1141 AN: 2641

East Asian (EAS) AF: 0.143 AC: 512 AN: 3571

South Asian (SAS) AF: 0.228 AC: 605 AN: 2659

European-Finnish (FIN) AF: 0.482 AC: 2761 AN: 5730

Middle Eastern (MID) AF: 0.405 AC: 85 AN: 210

European-Non Finnish (NFE) AF: 0.374 AC: 19737 AN: 52833

Other (OTH) AF: 0.437 AC: 651 AN: 1491

Alfa AF: 0.251 Hom.: 1094

Bravo AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.35
PhyloP100		-0.77
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: rs179016; hg19: chrX-12894442;