rs3764879

Positions:

• chrX-12906578-C-G
• chrX-12906578-C-T

Variant summary

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

The NR_030727.1(TLR8-AS1):​n.359-327G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 507,932 control chromosomes in the GnomAD database, including 19,535 homozygotes. There are 42,208 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 0.30 (4085 hom., 10265 hem., cov: 24)
  • Exomes 𝑓: 0.30 (15450 hom. 31943 hem.)
• Consequence: TLR8-AS1 NR_030727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

Genes affected

TLR8-AS1 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR8-AS1	NR_030727.1	n.359-327G>C		intron_variant
TLR8	NM_138636.5	c.-129C>G		upstream_gene_variant		ENST00000218032.7	NP_619542.1
TLR8	NM_016610.4	c.-212C>G		upstream_gene_variant			NP_057694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR8-AS1	ENST00000451564.1	n.119-327G>C		intron_variant		5
TLR8	ENST00000218032.7	c.-129C>G		upstream_gene_variant		1	NM_138636.5	ENSP00000218032.7

Frequencies

GnomAD3 genomes AF: 0.304 AC: 33787 AN: 111234 Hom.: 4088 Cov.: 24 AF XY: 0.306 AC XY: 10235 AN XY: 33468

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.299 AC: 118432 AN: 396643 Hom.: 15450 Cov.: 6 AF XY: 0.314 AC XY: 31943 AN XY: 101763

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.794

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.304 AC: 33815 AN: 111289 Hom.: 4085 Cov.: 24 AF XY: 0.306 AC XY: 10265 AN XY: 33533

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.343

Alfa AF: 0.263 Hom.: 1680

Bravo AF: 0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764879; hg19: chrX-12924697;