chrX-12871850-A-C

Position:

• chrX-12871850-A-C

Variant summary

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

The NM_016562.4(TLR7):​c.3+4269A>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 0.80 (25042 hom., 25703 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR7	NM_016562.4	c.3+4269A>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.3+4269A>C		intron_variant		1	NM_016562.4	ENSP00000370034	P1
TLR7	ENST00000484204.1	n.103+4269A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.799 AC: 87913 AN: 109995 Hom.: 25052 Cov.: 22 AF XY: 0.796 AC XY: 25641 AN XY: 32231

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.853

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.815

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: 0.799 AC: 87960 AN: 110048 Hom.: 25042 Cov.: 22 AF XY: 0.796 AC XY: 25703 AN XY: 32294

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.813

Alfa AF: 0.772 Hom.: 75712

Bravo AF: 0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.55

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: rs179019; hg19: chrX-12889969;