dbSNP rs2159377: TLR8:p.Asp118Asp (chrX-12919394-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_138636.5(TLR8):c.354C>T(p.Asp118Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,208,912 control chromosomes in the GnomAD database, including 22,885 homozygotes. There are 87,606 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 2196 hom., 7023 hem., cov: 22)

Exomes 𝑓: 0.21 ( 20689 hom. 80583 hem. )

Consequence

TLR8
NM_138636.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.289

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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant X-12919394-C-T is Benign according to our data. Variant chrX-12919394-C-T is described in ClinVar as [Benign]. Clinvar id is 2688225.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.289 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR8	NM_138636.5 link	c.354C>T	p.Asp118Asp	synonymous_variant	Exon 2 of 2	ENST00000218032.7	NP_619542.1	Q9NR97-1
TLR8	NM_016610.4 link	c.408C>T	p.Asp136Asp	synonymous_variant	Exon 3 of 3		NP_057694.2	Q9NR97-2
TLR8-AS1	NR_030727.1 link	n.241-11061G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7 link	c.354C>T	p.Asp118Asp	synonymous_variant	Exon 2 of 2	1	NM_138636.5	ENSP00000218032.7		Q9NR97-1
TLR8	ENST00000311912.5 link	c.408C>T	p.Asp136Asp	synonymous_variant	Exon 3 of 3	1		ENSP00000312082.5		Q9NR97-2

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

23049

AN:

110957

Hom.:

2196

Cov.:

AF XY:

0.211

AC XY:

7011

AN XY:

33179

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.379

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.226

GnomAD3 exomes

AF:

0.277

AC:

50483

AN:

182117

Hom.:

6103

AF XY:

0.285

AC XY:

19158

AN XY:

67131

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.760

Gnomad SAS exome

AF:

0.470

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.213

AC:

233349

AN:

1097902

Hom.:

20689

Cov.:

AF XY:

0.222

AC XY:

80583

AN XY:

363326

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.346

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.748

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.208

AC:

23059

AN:

111010

Hom.:

2196

Cov.:

AF XY:

0.211

AC XY:

7023

AN XY:

33242

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.748

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.178

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.198

Hom.:

16480

Bravo

AF:

0.223

EpiCase

AF:

0.189

EpiControl

AF:

0.192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.016

DANN

Benign

0.26

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over