rs4830805

Positions:

• chrX-12909640-G-A
• chrX-12909640-G-T

Variant summary

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

The ENST00000218032.7(TLR8):​c.3+2931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 110,800 control chromosomes in the GnomAD database, including 3,275 homozygotes. There are 8,910 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 0.27 (3275 hom., 8910 hem., cov: 23)
• Consequence: TLR8 ENST00000218032.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR8	NM_138636.5	c.3+2931G>A		intron_variant		ENST00000218032.7	NP_619542.1
TLR8-AS1	NR_030727.1	n.241-1307C>T		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4	c.-80-666G>A		intron_variant			NP_057694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.3+2931G>A		intron_variant		1	NM_138636.5	ENSP00000218032	P2
TLR8	ENST00000311912.5	c.-80-666G>A		intron_variant		1		ENSP00000312082	A2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 29851 AN: 110744 Hom.: 3277 Cov.: 23 AF XY: 0.270 AC XY: 8894 AN XY: 32996

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.270 AC: 29870 AN: 110800 Hom.: 3275 Cov.: 23 AF XY: 0.269 AC XY: 8910 AN XY: 33062

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.312

Alfa AF: 0.244 Hom.: 2454

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.62

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: rs4830805; hg19: chrX-12927759;