rs17256081

Positions:

• chrX-12907926-T-C

Variant summary

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

The NM_138636.5(TLR8):​c.3+1217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 111,171 control chromosomes in the GnomAD database, including 5,751 homozygotes. There are 11,839 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 0.37 (5751 hom., 11839 hem., cov: 23)
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR8	NM_138636.5	c.3+1217T>C		intron_variant		ENST00000218032.7	NP_619542.1
TLR8	NM_016610.4	c.-81+1217T>C		intron_variant			NP_057694.2
TLR8-AS1	NR_030727.1	n.358+290A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.3+1217T>C		intron_variant		1	NM_138636.5	ENSP00000218032.7
TLR8	ENST00000311912.5	c.-81+1217T>C		intron_variant		1		ENSP00000312082.5
TLR8-AS1	ENST00000451564.1	n.118+290A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.366 AC: 40688 AN: 111115 Hom.: 5753 Cov.: 23 AF XY: 0.355 AC XY: 11823 AN XY: 33349

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.366 AC: 40694 AN: 111171 Hom.: 5751 Cov.: 23 AF XY: 0.354 AC XY: 11839 AN XY: 33415

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.339

Alfa AF: 0.426 Hom.: 4494

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.75

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: rs17256081; hg19: chrX-12926045;