X-12885361-A-G

Position:

• chrX-12885361-A-G

Variant summary

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

The NM_016562.4(TLR7):​c.4-151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 497,934 control chromosomes in the GnomAD database, including 8,349 homozygotes. There are 31,188 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 0.21 (1788 hom., 7032 hem., cov: 23)
  • Exomes 𝑓: 0.21 (6561 hom. 24156 hem.)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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]

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 (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR7	NM_016562.4	c.4-151A>G		intron_variant		ENST00000380659.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR7	ENST00000380659.4	c.4-151A>G		intron_variant		1	NM_016562.4	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 23453 AN: 111694 Hom.: 1785 Cov.: 23 AF XY: 0.207 AC XY: 7006 AN XY: 33882

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.210 AC: 81270 AN: 386183 Hom.: 6561 AF XY: 0.205 AC XY: 24156 AN XY: 117583

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.0801

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.210 AC: 23474 AN: 111751 Hom.: 1788 Cov.: 23 AF XY: 0.207 AC XY: 7032 AN XY: 33949

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.223

Alfa AF: 0.182 Hom.: 3191

Bravo AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.050
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs179009; hg19: chrX-12903480;