NM_138636.5:c.3+1217T>C

Variant names:

• chrX-12907926-T-C
• rs17256081
• NM_138636.5:c.3+1217T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138636.5(TLR8):​c.3+1217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 111,171 control chromosomes in the GnomAD database, including 5,751 homozygotes. There are 11,839 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 0.37 (5751 hom., 11839 hem., cov: 23)
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR8	NM_138636.5	c.3+1217T>C		intron_variant	Intron 1 of 1	ENST00000218032.7	NP_619542.1
TLR8	NM_016610.4	c.-81+1217T>C		intron_variant	Intron 1 of 2		NP_057694.2
TLR8-AS1	NR_030727.1	n.358+290A>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.3+1217T>C		intron_variant	Intron 1 of 1	1	NM_138636.5	ENSP00000218032.7
TLR8	ENST00000311912.5	c.-81+1217T>C		intron_variant	Intron 1 of 2	1		ENSP00000312082.5
TLR8-AS1	ENST00000451564.1	n.118+290A>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.366 AC: 40688 AN: 111115 Hom.: 5753 Cov.: 23

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.366 AC: 40694 AN: 111171 Hom.: 5751 Cov.: 23 AF XY: 0.354 AC XY: 11839 AN XY: 33415

African (AFR) AF: 0.252 AC: 7737 AN: 30691

American (AMR) AF: 0.314 AC: 3315 AN: 10560

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 777 AN: 2637

East Asian (EAS) AF: 0.158 AC: 561 AN: 3547

South Asian (SAS) AF: 0.309 AC: 829 AN: 2684

European-Finnish (FIN) AF: 0.471 AC: 2745 AN: 5830

Middle Eastern (MID) AF: 0.352 AC: 76 AN: 216

European-Non Finnish (NFE) AF: 0.453 AC: 23954 AN: 52831

Other (OTH) AF: 0.339 AC: 511 AN: 1506

Alfa AF: 0.426 Hom.: 4494

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		0.27
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: rs17256081; hg19: chrX-12926045;