X-12884766-T-C

Position:

• chrX-12884766-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016562.4(TLR7):​c.4-746T>C 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 0.73 (21523 hom., 24154 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR7	NM_016562.4	c.4-746T>C		intron_variant		ENST00000380659.4	NP_057646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4	c.4-746T>C		intron_variant		1	NM_016562.4	ENSP00000370034	P1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 81520 AN: 111128 Hom.: 21522 Cov.: 23 AF XY: 0.723 AC XY: 24094 AN XY: 33306

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.705

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.734

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: 0.734 AC: 81581 AN: 111183 Hom.: 21523 Cov.: 23 AF XY: 0.724 AC XY: 24154 AN XY: 33371

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.732

Alfa AF: 0.700 Hom.: 45814

Bravo AF: 0.758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.46

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: rs179010; hg19: chrX-12902885;