dbSNP rs5744088: TLR8:c.*279G>C (chrX-12922445-G-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.*279G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 306,213 control chromosomes in the GnomAD database, including 3,155 homozygotes. There are 13,824 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 0.16 ( 1016 hom., 5104 hem., cov: 22)

Exomes 𝑓: 0.17 ( 2139 hom. 8720 hem. )

Consequence

TLR8
NM_138636.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.408

Publications

16 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:

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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TLR8	NM_138636.5 link	c.*279G>C	3_prime_UTR_variant	Exon 2 of 2	ENST00000218032.7	NP_619542.1
TLR8	NM_016610.4 link	c.*279G>C	3_prime_UTR_variant	Exon 3 of 3		NP_057694.2
TLR8-AS1	NR_030727.1 link	n.241-14112C>G	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7 link	c.*279G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_138636.5	ENSP00000218032.7
TLR8	ENST00000311912.5 link	c.*279G>C		downstream_gene_variant		1		ENSP00000312082.5

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

17443

AN:

110876

Hom.:

1015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.0382

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0499

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.178

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.159

GnomAD4 exome

AF:

0.169

AC:

32962

AN:

195283

Hom.:

2139

Cov.:

AF XY:

0.191

AC XY:

8720

AN XY:

45627

show subpopulations

African (AFR)

AF:

0.143

AC:

870

AN:

6094

American (AMR)

AF:

0.272

AC:

1941

AN:

7133

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

1095

AN:

6301

East Asian (EAS)

AF:

0.0763

AC:

1094

AN:

14345

South Asian (SAS)

AF:

0.171

AC:

1662

AN:

9736

European-Finnish (FIN)

AF:

0.224

AC:

3107

AN:

13882

Middle Eastern (MID)

AF:

0.192

AC:

167

AN:

868

European-Non Finnish (NFE)

AF:

0.168

AC:

20816

AN:

124200

Other (OTH)

AF:

0.174

AC:

2210

AN:

12724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

923

1846

2770

3693

4616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.157

AC:

17456

AN:

110930

Hom.:

1016

Cov.:

AF XY:

0.154

AC XY:

5104

AN XY:

33190

show subpopulations

African (AFR)

AF:

0.133

AC:

4064

AN:

30522

American (AMR)

AF:

0.232

AC:

2419

AN:

10419

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

430

AN:

2642

East Asian (EAS)

AF:

0.0500

AC:

177

AN:

3537

South Asian (SAS)

AF:

0.137

AC:

360

AN:

2631

European-Finnish (FIN)

AF:

0.196

AC:

1156

AN:

5890

Middle Eastern (MID)

AF:

0.167

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.162

AC:

8547

AN:

52881

Other (OTH)

AF:

0.159

AC:

241

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

533

1066

1599

2132

2665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.173

Hom.:

972

Bravo

AF:

0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.8

(source)

DANN

Benign

0.82

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(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