X-12914215-C-T

Variant names:

• chrX-12914215-C-T
• rs4830808
• NM_138636.5:c.4-4829C>T

Variant summary

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

The NM_138636.5(TLR8):​c.4-4829C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 110,713 control chromosomes in the GnomAD database, including 2,035 homozygotes. There are 6,378 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 0.19 (2035 hom., 6378 hem., cov: 22)
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR8	NM_138636.5	c.4-4829C>T		intron_variant	Intron 1 of 1	ENST00000218032.7	NP_619542.1
TLR8	NM_016610.4	c.57+3773C>T		intron_variant	Intron 2 of 2		NP_057694.2
TLR8-AS1	NR_030727.1	n.241-5882G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7	c.4-4829C>T		intron_variant	Intron 1 of 1	1	NM_138636.5	ENSP00000218032.7
TLR8	ENST00000311912.5	c.57+3773C>T		intron_variant	Intron 2 of 2	1		ENSP00000312082.5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 21025 AN: 110660 Hom.: 2036 Cov.: 22

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.214

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.190 AC: 21030 AN: 110713 Hom.: 2035 Cov.: 22 AF XY: 0.194 AC XY: 6378 AN XY: 32959

African (AFR) AF: 0.0803 AC: 2449 AN: 30517

American (AMR) AF: 0.306 AC: 3187 AN: 10426

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 531 AN: 2637

East Asian (EAS) AF: 0.752 AC: 2587 AN: 3442

South Asian (SAS) AF: 0.462 AC: 1200 AN: 2596

European-Finnish (FIN) AF: 0.136 AC: 803 AN: 5885

Middle Eastern (MID) AF: 0.225 AC: 48 AN: 213

European-Non Finnish (NFE) AF: 0.183 AC: 9638 AN: 52807

Other (OTH) AF: 0.215 AC: 326 AN: 1513

Alfa AF: 0.194 Hom.: 6196

Bravo AF: 0.202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.69
PhyloP100		-0.96
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: rs4830808; hg19: chrX-12932334;