X-12914412-C-T

Variant names:

• chrX-12914412-C-T
• rs1013151
• NM_138636.5:c.4-4632C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138636.5(TLR8):​c.4-4632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.51 (10773 hom., 16543 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 10 publications found

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:40720): (TLR8 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR8	NM_138636.5	c.4-4632C>T		intron_variant	Intron 1 of 1	ENST00000218032.7	NP_619542.1
TLR8	NM_016610.4	c.57+3970C>T		intron_variant	Intron 2 of 2		NP_057694.2
TLR8-AS1	NR_030727.1	n.241-6079G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.4-4632C>T		intron_variant	Intron 1 of 1	1	NM_138636.5	ENSP00000218032.7
TLR8	ENST00000311912.5	c.57+3970C>T		intron_variant	Intron 2 of 2	1		ENSP00000312082.5

Frequencies

GnomAD3 genomes AF: 0.509 AC: 56074 AN: 110184 Hom.: 10769 Cov.: 22

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.520

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.509 AC: 56110 AN: 110237 Hom.: 10773 Cov.: 22 AF XY: 0.509 AC XY: 16543 AN XY: 32507

African (AFR) AF: 0.648 AC: 19603 AN: 30243

American (AMR) AF: 0.627 AC: 6506 AN: 10377

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1207 AN: 2630

East Asian (EAS) AF: 0.794 AC: 2752 AN: 3465

South Asian (SAS) AF: 0.619 AC: 1598 AN: 2583

European-Finnish (FIN) AF: 0.409 AC: 2361 AN: 5776

Middle Eastern (MID) AF: 0.476 AC: 101 AN: 212

European-Non Finnish (NFE) AF: 0.395 AC: 20861 AN: 52763

Other (OTH) AF: 0.524 AC: 791 AN: 1510

Alfa AF: 0.439 Hom.: 4827

Bravo AF: 0.537

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.72
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1013151; hg19: chrX-12932531;