chrX-12918829-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138636.5(TLR8):​c.4-215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 111,968 control chromosomes in the GnomAD database, including 772 homozygotes. There are 2,241 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 0.075 ( 772 hom., 2241 hem., cov: 23)

Consequence

TLR8
NM_138636.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.801

Publications

1 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TLR8NM_138636.5 linkc.4-215A>G intron_variant Intron 1 of 1 ENST00000218032.7 NP_619542.1 Q9NR97-1
TLR8NM_016610.4 linkc.58-215A>G intron_variant Intron 2 of 2 NP_057694.2 Q9NR97-2
TLR8-AS1NR_030727.1 linkn.241-10496T>C intron_variant Intron 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TLR8ENST00000218032.7 linkc.4-215A>G intron_variant Intron 1 of 1 1 NM_138636.5 ENSP00000218032.7 Q9NR97-1
TLR8ENST00000311912.5 linkc.58-215A>G intron_variant Intron 2 of 2 1 ENSP00000312082.5 Q9NR97-2

Frequencies

GnomAD3 genomes
AF:
0.0744
AC:
8330
AN:
111914
Hom.:
771
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.257
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0307
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00110
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00844
Gnomad NFE
AF:
0.000733
Gnomad OTH
AF:
0.0596
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0746
AC:
8355
AN:
111968
Hom.:
772
Cov.:
23
AF XY:
0.0655
AC XY:
2241
AN XY:
34208
show subpopulations
African (AFR)
AF:
0.258
AC:
7895
AN:
30634
American (AMR)
AF:
0.0307
AC:
326
AN:
10615
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2648
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3591
South Asian (SAS)
AF:
0.00110
AC:
3
AN:
2729
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6115
Middle Eastern (MID)
AF:
0.00926
AC:
2
AN:
216
European-Non Finnish (NFE)
AF:
0.000733
AC:
39
AN:
53207
Other (OTH)
AF:
0.0589
AC:
90
AN:
1529
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
232
464
697
929
1161
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
84
168
252
336
420
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0125
Hom.:
47
Bravo
AF:
0.0855

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
1.9
DANN
Benign
0.54
PhyloP100
-0.80
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

Publications

Other links and lift over

dbSNP: rs5741888; hg19: chrX-12936948; API