rs2109134

Variant names:

• chrX-12909067-T-A
• rs2109134
• NM_138636.5:c.3+2358T>A

Your query was ambiguous. Multiple possible variants found:

• chrX-12909067-T-A
• chrX-12909067-T-G

Variant summary

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

The NM_138636.5(TLR8):​c.3+2358T>A 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 0.91 (32285 hom., 29644 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 9 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=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138636.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	NM_138636.5	MANE Select	c.3+2358T>A		intron	N/A	NP_619542.1
	TLR8	NM_016610.4		c.-80-1239T>A		intron	N/A	NP_057694.2
	TLR8-AS1	NR_030727.1		n.241-734A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	ENST00000218032.7	TSL:1 MANE Select	c.3+2358T>A		intron	N/A	ENSP00000218032.7
	TLR8	ENST00000311912.5	TSL:1	c.-80-1239T>A		intron	N/A	ENSP00000312082.5

Frequencies

GnomAD3 genomes AF: 0.911 AC: 100432 AN: 110188 Hom.: 32288 Cov.: 22

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.862

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.910

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: 0.911 AC: 100483 AN: 110245 Hom.: 32285 Cov.: 22 AF XY: 0.914 AC XY: 29644 AN XY: 32421

African (AFR) AF: 0.879 AC: 26536 AN: 30204

American (AMR) AF: 0.938 AC: 9690 AN: 10327

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 2407 AN: 2627

East Asian (EAS) AF: 1.00 AC: 3511 AN: 3511

South Asian (SAS) AF: 0.943 AC: 2417 AN: 2563

European-Finnish (FIN) AF: 0.938 AC: 5415 AN: 5772

Middle Eastern (MID) AF: 0.858 AC: 181 AN: 211

European-Non Finnish (NFE) AF: 0.915 AC: 48356 AN: 52858

Other (OTH) AF: 0.911 AC: 1366 AN: 1499

Alfa AF: 0.915 Hom.: 8180

Bravo AF: 0.911

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.76
PhyloP100		-0.035
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: rs2109134; hg19: chrX-12927186;