Genetic Variant TLR8:c.3+1217T>C (chrX-12907926-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.270

Publications

8 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 links:

TLR8-AS1 (HGNC:40720): (TLR8 antisense RNA 1)

TLR8-AS1 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR8	NM_138636.5	MANE Select	c.3+1217T>C	intron	N/A	NP_619542.1	Q9NR97-1
TLR8	NM_016610.4		c.-81+1217T>C	intron	N/A	NP_057694.2
TLR8-AS1	NR_030727.1		n.358+290A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR8	ENST00000218032.7	TSL:1 MANE Select	c.3+1217T>C	intron	N/A	ENSP00000218032.7	Q9NR97-1
TLR8	ENST00000311912.5	TSL:1	c.-81+1217T>C	intron	N/A	ENSP00000312082.5	Q9NR97-2
TLR8-AS1	ENST00000451564.1	TSL:5	n.118+290A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

40688

AN:

111115

Hom.:

5753

Cov.:

show subpopulations

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.:

AF XY:

0.354

AC XY:

11839

AN XY:

33415

show subpopulations

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:

AN:

216

European-Non Finnish (NFE)

AF:

0.453

AC:

23954

AN:

52831

Other (OTH)

AF:

0.339

AC:

511

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

913

1825

2738

3650

4563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.426

Hom.:

4494

Bravo

AF:

0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.6

(source)

DANN

Benign

0.75

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over