rs1548731

Variant names:

• chrX-12909828-T-C
• rs1548731
• NM_138636.5:c.3+3119T>C

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+3119T>C 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 0.64 (17020 hom., 21314 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 19 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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR8	NM_138636.5	c.3+3119T>C		intron_variant	Intron 1 of 1	ENST00000218032.7	NP_619542.1
TLR8	NM_016610.4	c.-80-478T>C		intron_variant	Intron 1 of 2		NP_057694.2
TLR8-AS1	NR_030727.1	n.241-1495A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.3+3119T>C		intron_variant	Intron 1 of 1	1	NM_138636.5	ENSP00000218032.7
TLR8	ENST00000311912.5	c.-80-478T>C		intron_variant	Intron 1 of 2	1		ENSP00000312082.5

Frequencies

GnomAD3 genomes AF: 0.641 AC: 70960 AN: 110774 Hom.: 17026 Cov.: 23

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.695

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.664

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: 0.640 AC: 70983 AN: 110828 Hom.: 17020 Cov.: 23 AF XY: 0.645 AC XY: 21314 AN XY: 33034

African (AFR) AF: 0.386 AC: 11785 AN: 30509

American (AMR) AF: 0.766 AC: 8001 AN: 10448

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 1831 AN: 2645

East Asian (EAS) AF: 0.968 AC: 3435 AN: 3550

South Asian (SAS) AF: 0.849 AC: 2241 AN: 2640

European-Finnish (FIN) AF: 0.697 AC: 4046 AN: 5803

Middle Eastern (MID) AF: 0.688 AC: 148 AN: 215

European-Non Finnish (NFE) AF: 0.720 AC: 38029 AN: 52840

Other (OTH) AF: 0.666 AC: 996 AN: 1495

Alfa AF: 0.702 Hom.: 77856

Bravo AF: 0.636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.86
PhyloP100		-0.29
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: rs1548731; hg19: chrX-12927947;