rs2109134

chrX-12909067-T-AchrX-12909067-T-G

Variant summary

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

The NM_138636.5(TLR8):c.3+2358T>A 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 0.91 (32285 hom., 29644 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

Genes affected

TLR8 (HGNC:15632): (toll like receptor 8) 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. 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. The various TLRs exhibit different patterns of expression. This gene is predominantly expressed in lung and peripheral blood leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X. [provided by RefSeq, Jul 2008]

TLR8-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAd at 32288 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR8	NM_138636.5	c.3+2358T>A		intron_variant		ENST00000218032.7
TLR8-AS1	NR_030727.1	n.241-734A>T		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4	c.-80-1239T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR8	ENST00000218032.7	c.3+2358T>A		intron_variant		1	NM_138636.5	P2
TLR8	ENST00000311912.5	c.-80-1239T>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.911 AC: 100432 AN: 110188 Hom.: 32288 Cov.: 22 AF XY: 0.914 AC XY: 29585 AN XY: 32354

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.862

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.910

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: 0.911 AC: 100483 AN: 110245 Hom.: 32285 Cov.: 22 AF XY: 0.914 AC XY: 29644 AN XY: 32421

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.938

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.911

Alfa AF: 0.915 Hom.: 8180

Bravo AF: 0.911

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.76

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: rs2109134; hg19: chrX-12927186;