rs5741888

Positions:

• chrX-12918829-A-G
• chrX-12918829-A-T

Variant summary

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

The NM_138636.5(TLR8):​c.4-215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 111,968 control chromosomes in the GnomAD database, including 772 homozygotes. There are 2,241 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 0.075 (772 hom., 2241 hem., cov: 23)
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR8	NM_138636.5	c.4-215A>G		intron_variant		ENST00000218032.7	NP_619542.1
TLR8	NM_016610.4	c.58-215A>G		intron_variant			NP_057694.2
TLR8-AS1	NR_030727.1	n.241-10496T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.4-215A>G		intron_variant		1	NM_138636.5	ENSP00000218032.7
TLR8	ENST00000311912.5	c.58-215A>G		intron_variant		1		ENSP00000312082.5

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 8330 AN: 111914 Hom.: 771 Cov.: 23 AF XY: 0.0650 AC XY: 2219 AN XY: 34144

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00110

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.000733

Gnomad OTH AF: 0.0596

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

GnomAD4 genome AF: 0.0746 AC: 8355 AN: 111968 Hom.: 772 Cov.: 23 AF XY: 0.0655 AC XY: 2241 AN XY: 34208

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00110

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000733

Gnomad4 OTH AF: 0.0589

Alfa AF: 0.0125 Hom.: 47

Bravo AF: 0.0855

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.54

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: rs5741888; hg19: chrX-12936948;