chrX-12867459-T-G

Position:

• chrX-12867459-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016562.4(TLR7):​c.-98-22T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 604,443 control chromosomes in the GnomAD database, including 1,041 homozygotes. There are 13,252 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 0.054 (133 hom., 1895 hem., cov: 23)
  • Exomes 𝑓: 0.070 (908 hom. 11357 hem.)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR7	NM_016562.4	c.-98-22T>G		intron_variant		ENST00000380659.4	NP_057646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4	c.-98-22T>G		intron_variant		1	NM_016562.4	ENSP00000370034.3
TLR7	ENST00000484204.1	n.-20T>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 6037 AN: 111874 Hom.: 133 Cov.: 23 AF XY: 0.0555 AC XY: 1888 AN XY: 34026

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0502

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0418

GnomAD4 exome AF: 0.0704 AC: 34675 AN: 492517 Hom.: 908 Cov.: 8 AF XY: 0.0763 AC XY: 11357 AN XY: 148921

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.0903

Gnomad4 ASJ exome AF: 0.0708

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0740

Gnomad4 NFE exome AF: 0.0638

Gnomad4 OTH exome AF: 0.0641

GnomAD4 genome AF: 0.0540 AC: 6043 AN: 111926 Hom.: 133 Cov.: 23 AF XY: 0.0556 AC XY: 1895 AN XY: 34090

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.0616

Gnomad4 EAS AF: 0.0778

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0631

Gnomad4 OTH AF: 0.0413

Alfa AF: 0.0632 Hom.: 2255

Bravo AF: 0.0531

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2302267; hg19: chrX-12885578;