chrX-12883352-G-A

Position:

• chrX-12883352-G-A

Variant summary

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

The NM_016562.4(TLR7):​c.4-2160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 111,093 control chromosomes in the GnomAD database, including 1,329 homozygotes. There are 5,732 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 (1329 hom., 5732 hem., cov: 22)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR7	NM_016562.4	c.4-2160G>A		intron_variant		ENST00000380659.4	NP_057646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4	c.4-2160G>A		intron_variant		1	NM_016562.4	ENSP00000370034.3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 19466 AN: 111038 Hom.: 1330 Cov.: 22 AF XY: 0.172 AC XY: 5724 AN XY: 33270

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0107

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.175 AC: 19466 AN: 111093 Hom.: 1329 Cov.: 22 AF XY: 0.172 AC XY: 5732 AN XY: 33335

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0107

Gnomad4 SAS AF: 0.0515

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.176

Alfa AF: 0.199 Hom.: 12531

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.69

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: rs179013; hg19: chrX-12901471; COSMIC: COSV66124306;