X-12906578-C-G

Variant names:

• chrX-12906578-C-G
• rs3764879
• ENST00000451564.1:n.119-327G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 78 publications found

Genes affected

TLR8-AS1 (HGNC:40720): (TLR8 antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• immunodeficiency 98 with autoinflammation, X-linked

  Inheritance: Unknown, XL Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_030727.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8-AS1	NR_030727.1		n.359-327G>C		intron	N/A
	TLR8	NM_138636.5	MANE Select	c.-129C>G		upstream_gene	N/A	NP_619542.1	Q9NR97-1
	TLR8	NM_016610.4		c.-212C>G		upstream_gene	N/A	NP_057694.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8-AS1	ENST00000451564.1	TSL:5	n.119-327G>C		intron	N/A
	TLR8	ENST00000218032.7	TSL:1 MANE Select	c.-129C>G		upstream_gene	N/A	ENSP00000218032.7	Q9NR97-1
	TLR8	ENST00000311912.5	TSL:1	c.-212C>G		upstream_gene	N/A	ENSP00000312082.5	Q9NR97-2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 33787 AN: 111234 Hom.: 4088 Cov.: 24

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

African (AFR) AF: 0.261 AC: 2621 AN: 10046

American (AMR) AF: 0.513 AC: 6097 AN: 11881

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 3248 AN: 8383

East Asian (EAS) AF: 0.794 AC: 16547 AN: 20851

South Asian (SAS) AF: 0.509 AC: 4327 AN: 8505

European-Finnish (FIN) AF: 0.216 AC: 6622 AN: 30661

Middle Eastern (MID) AF: 0.383 AC: 931 AN: 2432

European-Non Finnish (NFE) AF: 0.252 AC: 71630 AN: 284320

Other (OTH) AF: 0.328 AC: 6409 AN: 19564

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

African (AFR) AF: 0.270 AC: 8250 AN: 30507

American (AMR) AF: 0.454 AC: 4752 AN: 10462

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1067 AN: 2633

East Asian (EAS) AF: 0.810 AC: 2851 AN: 3519

South Asian (SAS) AF: 0.526 AC: 1423 AN: 2706

European-Finnish (FIN) AF: 0.197 AC: 1180 AN: 5978

Middle Eastern (MID) AF: 0.357 AC: 76 AN: 213

European-Non Finnish (NFE) AF: 0.253 AC: 13435 AN: 53067

Other (OTH) AF: 0.343 AC: 524 AN: 1527

Alfa AF: 0.263 Hom.: 1680

Bravo AF: 0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.66
PhyloP100		-0.096
PromoterAI		-0.063	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3764879; hg19: chrX-12924697;