rs5979763

Positions:

• chrX-12922694-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.*528T>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 0.0731 in 112,418 control chromosomes in the GnomAD database, including 765 homozygotes. There are 2,150 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 0.073 (765 hom., 2148 hem., cov: 23)
  • Exomes 𝑓: 0.0075 (0 hom. 2 hem.)
• Consequence: TLR8 NM_138636.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR8	NM_138636.5	c.*528T>C		3_prime_UTR_variant	2/2	ENST00000218032.7
TLR8-AS1	NR_030727.1	n.241-14361A>G		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4	c.*528T>C		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR8	ENST00000218032.7	c.*528T>C		3_prime_UTR_variant	2/2	1	NM_138636.5	P2

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 8186 AN: 111835 Hom.: 764 Cov.: 23 AF XY: 0.0626 AC XY: 2128 AN XY: 34015

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000745

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0125

Gnomad NFE AF: 0.000752

Gnomad OTH AF: 0.0575

GnomAD4 exome AF: 0.00752 AC: 4 AN: 532 Hom.: 0 Cov.: 0 AF XY: 0.0263 AC XY: 2 AN XY: 76

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.0270

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0734 AC: 8209 AN: 111886 Hom.: 765 Cov.: 23 AF XY: 0.0630 AC XY: 2148 AN XY: 34076

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000747

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000752

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0519 Hom.: 340

Bravo AF: 0.0849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.78
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5979763; hg19: chrX-12940813;