Variant rs5744081 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:):

TLR8-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TLR8	NM_138636.5 linkuse as main transcript	c.1312C>A	p.Arg438Arg	synonymous_variant	2/2	ENST00000218032.7	NP_619542.1	Q9NR97-1
TLR8	NM_016610.4 linkuse as main transcript	c.1366C>A	p.Arg456Arg	synonymous_variant	3/3		NP_057694.2	Q9NR97-2
TLR8-AS1	NR_030727.1 linkuse as main transcript	n.241-12019G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7 linkuse as main transcript	c.1312C>A	p.Arg438Arg	synonymous_variant	2/2	1	NM_138636.5	ENSP00000218032.7		Q9NR97-1
TLR8	ENST00000311912.5 linkuse as main transcript	c.1366C>A	p.Arg456Arg	synonymous_variant	3/3	1		ENSP00000312082.5		Q9NR97-2

Frequencies

GnomAD3 genomes

AF:

0.0721

AC:

8080

AN:

112068

Hom.:

727

Cov.:

AF XY:

0.0633

AC XY:

2170

AN XY:

34272

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

GnomAD3 exomes

AF:

0.0203

AC:

3676

AN:

181459

Hom.:

326

AF XY:

0.0131

AC XY:

870

AN XY:

66215

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 SAS exome

AF:

0.000324

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

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000303

Gnomad4 OTH exome

AF:

0.0168

GnomAD4 genome

AF:

0.0722

AC:

8100

AN:

112120

Hom.:

728

Cov.:

AF XY:

0.0637

AC XY:

2187

AN XY:

34334

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.0295

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000732

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000619

Gnomad4 OTH

AF:

0.0551

Alfa

AF:

0.0126

Hom.:

714

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

DANN

Benign

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over