chrX-12872031-T-C

Variant names:

• chrX-12872031-T-C
• rs179018
• NM_016562.4:c.3+4450T>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+4450T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 110,248 control chromosomes in the GnomAD database, including 1,421 homozygotes. There are 5,652 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 0.18 (1421 hom., 5652 hem., cov: 21)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.3+4450T>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.3+4450T>C		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3
TLR7	ENST00000484204.1	n.103+4450T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 19886 AN: 110193 Hom.: 1422 Cov.: 21

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00991

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.164

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.180 AC: 19885 AN: 110248 Hom.: 1421 Cov.: 21 AF XY: 0.174 AC XY: 5652 AN XY: 32538

African (AFR) AF: 0.120 AC: 3637 AN: 30417

American (AMR) AF: 0.214 AC: 2224 AN: 10373

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 431 AN: 2630

East Asian (EAS) AF: 0.00994 AC: 35 AN: 3522

South Asian (SAS) AF: 0.0652 AC: 170 AN: 2606

European-Finnish (FIN) AF: 0.266 AC: 1524 AN: 5720

Middle Eastern (MID) AF: 0.157 AC: 34 AN: 217

European-Non Finnish (NFE) AF: 0.217 AC: 11415 AN: 52588

Other (OTH) AF: 0.178 AC: 267 AN: 1497

Alfa AF: 0.211 Hom.: 1881

Bravo AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.65
PhyloP100		-0.47
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: rs179018; hg19: chrX-12890150;