dbSNP rs5744081: TLR8:p.Arg438Arg (chrX-12920352-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_138636.5(TLR8):c.1312C>A(p.Arg438Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,209,090 control chromosomes in the GnomAD database, including 1,427 homozygotes. There are 4,331 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 0.072 ( 728 hom., 2187 hem., cov: 23)

Exomes 𝑓: 0.0076 ( 699 hom. 2144 hem. )

Consequence

TLR8
NM_138636.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.659

Publications

6 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-0.659 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR8	NM_138636.5 link	c.1312C>A	p.Arg438Arg	synonymous_variant	Exon 2 of 2	ENST00000218032.7	NP_619542.1	Q9NR97-1
TLR8	NM_016610.4 link	c.1366C>A	p.Arg456Arg	synonymous_variant	Exon 3 of 3		NP_057694.2	Q9NR97-2
TLR8-AS1	NR_030727.1 link	n.241-12019G>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7 link	c.1312C>A	p.Arg438Arg	synonymous_variant	Exon 2 of 2	1	NM_138636.5	ENSP00000218032.7		Q9NR97-1
TLR8	ENST00000311912.5 link	c.1366C>A	p.Arg456Arg	synonymous_variant	Exon 3 of 3	1		ENSP00000312082.5		Q9NR97-2

Frequencies

GnomAD3 genomes

AF:

0.0721

AC:

8080

AN:

112068

Hom.:

727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000729

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000619

Gnomad OTH

AF:

0.0558

GnomAD2 exomes

AF:

0.0203

AC:

3676

AN:

181459

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000406

Gnomad OTH exome

AF:

0.00693

GnomAD4 exome

AF:

0.00763

AC:

8373

AN:

1096970

Hom.:

699

Cov.:

AF XY:

0.00592

AC XY:

2144

AN XY:

362438

show subpopulations

African (AFR)

AF:

0.259

AC:

6814

AN:

26335

American (AMR)

AF:

0.0135

AC:

472

AN:

35073

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19365

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30181

South Asian (SAS)

AF:

0.000464

AC:

AN:

53877

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40418

Middle Eastern (MID)

AF:

0.00727

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.000303

AC:

255

AN:

841547

Other (OTH)

AF:

0.0168

AC:

775

AN:

46045

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

278

556

833

1111

1389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<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:

0.0722

AC:

8100

AN:

112120

Hom.:

728

Cov.:

AF XY:

0.0637

AC XY:

2187

AN XY:

34334

show subpopulations

African (AFR)

AF:

0.249

AC:

7664

AN:

30736

American (AMR)

AF:

0.0295

AC:

313

AN:

10621

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3609

South Asian (SAS)

AF:

0.000732

AC:

AN:

2733

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6056

Middle Eastern (MID)

AF:

0.0140

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.000619

AC:

AN:

53269

Other (OTH)

AF:

0.0551

AC:

AN:

1543

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

245

490

735

980

1225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0290

Hom.:

2358

Bravo

AF:

0.0828

EpiCase

AF:

0.000437

EpiControl

AF:

0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.20

(source)

DANN

Benign

0.38

PhyloP100

-0.66

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over