dbSNP rs3764879: TLR8-AS1:n.119-327G>C (chrX-12906578-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000451564.1(TLR8-AS1):n.119-327G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 507,932 control chromosomes in the GnomAD database, including 19,535 homozygotes. There are 42,208 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 0.30 ( 4085 hom., 10265 hem., cov: 24)

Exomes 𝑓: 0.30 ( 15450 hom. 31943 hem. )

Consequence

TLR8-AS1
ENST00000451564.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960

Publications

74 publications found

Variant links:

Genes affected

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

TLR8-AS1 links:

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 Gene-Disease associations (from GenCC):

immunodeficiency 98 with autoinflammation, X-linked
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TLR8 links:

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TLR8-AS1	NR_030727.1 link	n.359-327G>C	intron_variant	Intron 3 of 4
TLR8	NM_138636.5 link	c.-129C>G	upstream_gene_variant		ENST00000218032.7	NP_619542.1	Q9NR97-1
TLR8	NM_016610.4 link	c.-212C>G	upstream_gene_variant			NP_057694.2	Q9NR97-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TLR8-AS1	ENST00000451564.1 link	n.119-327G>C	intron_variant	Intron 1 of 2	5
TLR8	ENST00000218032.7 link	c.-129C>G	upstream_gene_variant		1	NM_138636.5	ENSP00000218032.7	Q9NR97-1
TLR8	ENST00000311912.5 link	c.-212C>G	upstream_gene_variant		1		ENSP00000312082.5	Q9NR97-2

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

33787

AN:

111234

Hom.:

4088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.810

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.299

AC:

118432

AN:

396643

Hom.:

15450

Cov.:

AF XY:

0.314

AC XY:

31943

AN XY:

101763

show subpopulations

African (AFR)

AF:

0.261

AC:

2621

AN:

10046

American (AMR)

AF:

0.513

AC:

6097

AN:

11881

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

3248

AN:

8383

East Asian (EAS)

AF:

0.794

AC:

16547

AN:

20851

South Asian (SAS)

AF:

0.509

AC:

4327

AN:

8505

European-Finnish (FIN)

AF:

0.216

AC:

6622

AN:

30661

Middle Eastern (MID)

AF:

0.383

AC:

931

AN:

2432

European-Non Finnish (NFE)

AF:

0.252

AC:

71630

AN:

284320

Other (OTH)

AF:

0.328

AC:

6409

AN:

19564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

2784

5568

8352

11136

13920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2144

4288

6432

8576

10720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.304

AC:

33815

AN:

111289

Hom.:

4085

Cov.:

AF XY:

0.306

AC XY:

10265

AN XY:

33533

show subpopulations

African (AFR)

AF:

0.270

AC:

8250

AN:

30507

American (AMR)

AF:

0.454

AC:

4752

AN:

10462

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1067

AN:

2633

East Asian (EAS)

AF:

0.810

AC:

2851

AN:

3519

South Asian (SAS)

AF:

0.526

AC:

1423

AN:

2706

European-Finnish (FIN)

AF:

0.197

AC:

1180

AN:

5978

Middle Eastern (MID)

AF:

0.357

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.253

AC:

13435

AN:

53067

Other (OTH)

AF:

0.343

AC:

524

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

804

1607

2411

3214

4018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.263

Hom.:

1680

Bravo

AF:

0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.3

(source)

DANN

Benign

0.66

PhyloP100

-0.096

PromoterAI

-0.063

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over