rs5744068

Positions:

• chrX-12916939-C-T

Variant summary

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

The NM_138636.5(TLR8):​c.4-2105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 111,159 control chromosomes in the GnomAD database, including 956 homozygotes. There are 5,061 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 0.15 (956 hom., 5061 hem., cov: 22)
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR8	NM_138636.5	c.4-2105C>T		intron_variant		ENST00000218032.7	NP_619542.1
TLR8-AS1	NR_030727.1	n.241-8606G>A		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4	c.58-2105C>T		intron_variant			NP_057694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.4-2105C>T		intron_variant		1	NM_138636.5	ENSP00000218032	P2
TLR8	ENST00000311912.5	c.58-2105C>T		intron_variant		1		ENSP00000312082	A2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 16948 AN: 111105 Hom.: 956 Cov.: 22 AF XY: 0.152 AC XY: 5053 AN XY: 33303

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0412

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.153 AC: 16952 AN: 111159 Hom.: 956 Cov.: 22 AF XY: 0.152 AC XY: 5061 AN XY: 33367

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.162

Alfa AF: 0.165 Hom.: 8438

Bravo AF: 0.156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.58

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: rs5744068; hg19: chrX-12935058;