rs5744088

Positions:

• chrX-12922445-G-C
• chrX-12922445-G-T

Variant summary

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

The NM_138636.5(TLR8):​c.*279G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 306,213 control chromosomes in the GnomAD database, including 3,155 homozygotes. There are 13,824 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 0.16 (1016 hom., 5104 hem., cov: 22)
  • Exomes 𝑓: 0.17 (2139 hom. 8720 hem.)
• Consequence: TLR8 NM_138636.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR8	NM_138636.5	c.*279G>C		3_prime_UTR_variant	2/2	ENST00000218032.7	NP_619542.1
TLR8-AS1	NR_030727.1	n.241-14112C>G		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4	c.*279G>C		3_prime_UTR_variant	3/3		NP_057694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.*279G>C		3_prime_UTR_variant	2/2	1	NM_138636.5	ENSP00000218032	P2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 17443 AN: 110876 Hom.: 1015 Cov.: 22 AF XY: 0.154 AC XY: 5089 AN XY: 33126

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0382

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.169 AC: 32962 AN: 195283 Hom.: 2139 Cov.: 2 AF XY: 0.191 AC XY: 8720 AN XY: 45627

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.0763

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.157 AC: 17456 AN: 110930 Hom.: 1016 Cov.: 22 AF XY: 0.154 AC XY: 5104 AN XY: 33190

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.159

Alfa AF: 0.173 Hom.: 972

Bravo AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5744088; hg19: chrX-12940564;