rs179014

chrX-12881646-A-GchrX-12881646-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_016562.4(TLR7):c.4-3866A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.85 (28226 hom., 24172 hem., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd at 28228 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR7	NM_016562.4	c.4-3866A>G		intron_variant		ENST00000380659.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR7	ENST00000380659.4	c.4-3866A>G		intron_variant		1	NM_016562.4	P1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 89768 AN: 105695 Hom.: 28228 Cov.: 19 AF XY: 0.846 AC XY: 24136 AN XY: 28531

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.871

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.871

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.849 AC: 89798 AN: 105718 Hom.: 28226 Cov.: 19 AF XY: 0.846 AC XY: 24172 AN XY: 28564

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.929

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.873

Alfa AF: 0.820 Hom.: 7570

Bravo AF: 0.869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.45

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: rs179014; hg19: chrX-12899765;