Variant chr4-38797314-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003263.4(TLR1):c.1518G>A(p.Ser506Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,613,154 control chromosomes in the GnomAD database, including 86,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.42 ( 17926 hom., cov: 31)

Exomes 𝑓: 0.27 ( 68101 hom. )

Consequence

TLR1
NM_003263.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.13

Variant links:

Genes affected

TLR1 (HGNC:11847): (toll like receptor 1) 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 ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

TLR1 links:

TLR1 (HGNC:):

TLR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-38797314-C-T is Benign according to our data. Variant chr4-38797314-C-T is described in ClinVar as [Benign]. Clinvar id is 3059108.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	NM_003263.4 linkuse as main transcript	c.1518G>A	p.Ser506Ser	synonymous_variant	4/4	ENST00000308979.7	NP_003254.2	Q15399

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TLR1	ENST00000308979.7 linkuse as main transcript	c.1518G>A	p.Ser506Ser	synonymous_variant	4/4	1	NM_003263.4	ENSP00000354932.2	Q15399
TLR1	ENST00000502213.6 linkuse as main transcript	c.1518G>A	p.Ser506Ser	synonymous_variant	3/3	1		ENSP00000421259.1	Q15399
TLR1	ENST00000505744.5 linkuse as main transcript	n.235+3543G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64368

AN:

151766

Hom.:

17883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.596

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.469

GnomAD3 exomes

AF:

0.376

AC:

94350

AN:

250704

Hom.:

21752

AF XY:

0.370

AC XY:

50255

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.762

Gnomad AMR exome

AF:

0.513

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.593

Gnomad SAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.270

AC:

394851

AN:

1461270

Hom.:

68101

Cov.:

AF XY:

0.276

AC XY:

200542

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.756

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.632

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.323

GnomAD4 genome

AF:

0.424

AC:

64466

AN:

151884

Hom.:

17926

Cov.:

AF XY:

0.424

AC XY:

31457

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.756

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.410

Gnomad4 EAS

AF:

0.595

Gnomad4 SAS

AF:

0.483

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.472

Alfa

AF:

0.226

Hom.:

994

Bravo

AF:

0.467

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TLR1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.27

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