Variant rs3747414 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138636.5(TLR8):c.2253C>A(p.Ile751=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,208,493 control chromosomes in the GnomAD database, including 63,258 homozygotes. There are 154,763 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 6242 hom., 13057 hem., cov: 23)

Exomes 𝑓: 0.38 ( 57016 hom. 141706 hem. )

Consequence

TLR8
NM_138636.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.177

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-12921293-C-A is Benign according to our data. Variant chrX-12921293-C-A is described in ClinVar as [Benign]. Clinvar id is 2688012.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.177 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TLR8	NM_138636.5 linkuse as main transcript	c.2253C>A	p.Ile751=	synonymous_variant	2/2	ENST00000218032.7
TLR8-AS1	NR_030727.1 linkuse as main transcript	n.241-12960G>T		intron_variant, non_coding_transcript_variant
TLR8	NM_016610.4 linkuse as main transcript	c.2307C>A	p.Ile769=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR8	ENST00000218032.7 linkuse as main transcript	c.2253C>A	p.Ile751=	synonymous_variant	2/2	1	NM_138636.5	P2	Q9NR97-1
TLR8	ENST00000311912.5 linkuse as main transcript	c.2307C>A	p.Ile769=	synonymous_variant	3/3	1		A2	Q9NR97-2

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

43353

AN:

110447

Hom.:

6242

Cov.:

AF XY:

0.398

AC XY:

13027

AN XY:

32733

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.552

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.422

GnomAD3 exomes

AF:

0.458

AC:

83370

AN:

182106

Hom.:

13672

AF XY:

0.457

AC XY:

30645

AN XY:

67012

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.642

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.802

Gnomad SAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.422

GnomAD4 exome

AF:

0.383

AC:

420144

AN:

1097992

Hom.:

57016

Cov.:

AF XY:

0.390

AC XY:

141706

AN XY:

363416

show subpopulations

Gnomad4 AFR exome

AF:

0.374

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.808

Gnomad4 SAS exome

AF:

0.603

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.408

GnomAD4 genome

AF:

0.393

AC:

43380

AN:

110501

Hom.:

6242

Cov.:

AF XY:

0.398

AC XY:

13057

AN XY:

32797

show subpopulations

Gnomad4 AFR

AF:

0.369

Gnomad4 AMR

AF:

0.552

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.800

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.342

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.368

Hom.:

23533

Bravo

AF:

0.413

EpiCase

AF:

0.341

EpiControl

AF:

0.352

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 72% of patients studied by a panel of primary immunodeficiencies. Number of patients: 68. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.7

DANN

Benign

0.58

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