Variant chrX-12920993-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000218032.7(TLR8):c.1953G>C(p.Leu651=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,097,489 control chromosomes in the GnomAD database, including 77,982 homozygotes. There are 163,025 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.58 ( 15140 hom., 18927 hem., cov: 23)

Exomes 𝑓: 0.45 ( 77982 hom. 163025 hem. )

Failed GnomAD Quality Control

Consequence

TLR8
ENST00000218032.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.61

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=-0.94).

BP6

Variant X-12920993-G-C is Benign according to our data. Variant chrX-12920993-G-C is described in ClinVar as [Benign]. Clinvar id is 2687998.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.61 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TLR8	NM_138636.5 linkuse as main transcript	c.1953G>C	p.Leu651=	synonymous_variant	2/2	ENST00000218032.7	NP_619542.1
TLR8-AS1	NR_030727.1 linkuse as main transcript	n.241-12660C>G		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4 linkuse as main transcript	c.2007G>C	p.Leu669=	synonymous_variant	3/3		NP_057694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR8	ENST00000218032.7 linkuse as main transcript	c.1953G>C	p.Leu651=	synonymous_variant	2/2	1	NM_138636.5	ENSP00000218032	P2	Q9NR97-1
TLR8	ENST00000311912.5 linkuse as main transcript	c.2007G>C	p.Leu669=	synonymous_variant	3/3	1		ENSP00000312082	A2	Q9NR97-2

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

64079

AN:

110555

Hom.:

15138

Cov.:

AF XY:

0.575

AC XY:

18867

AN XY:

32801

show subpopulations

Gnomad AFR

AF:

0.895

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.642

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.575

GnomAD3 exomes

AF:

0.541

AC:

98712

AN:

182621

Hom.:

19374

AF XY:

0.526

AC XY:

35415

AN XY:

67315

show subpopulations

Gnomad AFR exome

AF:

0.905

Gnomad AMR exome

AF:

0.687

Gnomad ASJ exome

AF:

0.469

Gnomad EAS exome

AF:

0.807

Gnomad SAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.431

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.445

AC:

488543

AN:

1097489

Hom.:

77982

Cov.:

AF XY:

0.449

AC XY:

163025

AN XY:

363003

show subpopulations

Gnomad4 AFR exome

AF:

0.906

Gnomad4 AMR exome

AF:

0.685

Gnomad4 ASJ exome

AF:

0.467

Gnomad4 EAS exome

AF:

0.810

Gnomad4 SAS exome

AF:

0.641

Gnomad4 FIN exome

AF:

0.437

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.491

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.580

AC:

64141

AN:

110608

Hom.:

15140

Cov.:

AF XY:

0.576

AC XY:

18927

AN XY:

32864

show subpopulations

Gnomad4 AFR

AF:

0.895

Gnomad4 AMR

AF:

0.643

Gnomad4 ASJ

AF:

0.478

Gnomad4 EAS

AF:

0.804

Gnomad4 SAS

AF:

0.644

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.578

Alfa

AF:

0.469

Hom.:

4913

Bravo

AF:

0.615

EpiCase

AF:

0.388

EpiControl

AF:

0.403

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 75% of patients studied by a panel of primary immunodeficiencies. Number of patients: 71. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.042

DANN

Benign

0.40

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