X-12919685-C-T

Variant summary

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

The NM_138636.5(TLR8):c.645C>T(p.His215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,097,286 control chromosomes in the GnomAD database, including 74,596 homozygotes. There are 160,196 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 12589 hom., 17416 hem., cov: 22)

Exomes 𝑓: 0.44 ( 74596 hom. 160196 hem. )

Failed GnomAD Quality Control

Consequence

TLR8
NM_138636.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.52

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:

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=-0.79).

BP6

Variant X-12919685-C-T is Benign according to our data. Variant chrX-12919685-C-T is described in ClinVar as [Benign]. Clinvar id is 2688009.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.52 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TLR8	NM_138636.5 linkuse as main transcript	c.645C>T	p.His215=	synonymous_variant	2/2	ENST00000218032.7
TLR8-AS1	NR_030727.1 linkuse as main transcript	n.241-11352G>A		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4 linkuse as main transcript	c.699C>T	p.His233=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR8	ENST00000218032.7 linkuse as main transcript	c.645C>T	p.His215=	synonymous_variant	2/2	1	NM_138636.5	P2	Q9NR97-1
TLR8	ENST00000311912.5 linkuse as main transcript	c.699C>T	p.His233=	synonymous_variant	3/3	1		A2	Q9NR97-2

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

59381

AN:

110085

Hom.:

12582

Cov.:

AF XY:

0.537

AC XY:

17356

AN XY:

32329

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.460

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.543

GnomAD3 exomes

AF:

0.524

AC:

95416

AN:

182112

Hom.:

17853

AF XY:

0.510

AC XY:

34158

AN XY:

66926

show subpopulations

Gnomad AFR exome

AF:

0.769

Gnomad AMR exome

AF:

0.679

Gnomad ASJ exome

AF:

0.465

Gnomad EAS exome

AF:

0.800

Gnomad SAS exome

AF:

0.627

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.492

GnomAD4 exome

AF:

0.438

AC:

480707

AN:

1097286

Hom.:

74596

Cov.:

AF XY:

0.442

AC XY:

160196

AN XY:

362736

show subpopulations

Gnomad4 AFR exome

AF:

0.777

Gnomad4 AMR exome

AF:

0.678

Gnomad4 ASJ exome

AF:

0.465

Gnomad4 EAS exome

AF:

0.807

Gnomad4 SAS exome

AF:

0.616

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.390

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.540

AC:

59447

AN:

110139

Hom.:

12589

Cov.:

AF XY:

0.538

AC XY:

17416

AN XY:

32393

show subpopulations

Gnomad4 AFR

AF:

0.766

Gnomad4 AMR

AF:

0.626

Gnomad4 ASJ

AF:

0.477

Gnomad4 EAS

AF:

0.799

Gnomad4 SAS

AF:

0.622

Gnomad4 FIN

AF:

0.401

Gnomad4 NFE

AF:

0.390

Gnomad4 OTH

AF:

0.546

Alfa

AF:

0.420

Hom.:

20544

Bravo

AF:

0.571

EpiCase

AF:

0.385

EpiControl

AF:

0.399

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.0080

Dann

Benign

0.69

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