Variant 11-1291476-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019009.4(TOLLIP):c.184-1067G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 150,258 control chromosomes in the GnomAD database, including 1,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance,association (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1480 hom., cov: 24)

Consequence

TOLLIP
NM_019009.4 intron

Scores

Clinical Significance

Uncertain significance; association no assertion criteria provided U:3O:1

Conservation

PhyloP100: 0.0880

Variant links:

Genes affected

TOLLIP (HGNC:16476): (toll interacting protein) This gene encodes a ubiquitin-binding protein that interacts with several Toll-like receptor (TLR) signaling cascade components. The encoded protein regulates inflammatory signaling and is involved in interleukin-1 receptor trafficking and in the turnover of IL1R-associated kinase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

TOLLIP links:

TOLLIP (HGNC:):

TOLLIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOLLIP	NM_019009.4 linkuse as main transcript	c.184-1067G>C		intron_variant		ENST00000317204.11	NP_061882.2	Q9H0E2-1Q6FIE9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11 linkuse as main transcript	c.184-1067G>C		intron_variant		1	NM_019009.4	ENSP00000314733.5		Q9H0E2-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18402

AN:

150142

Hom.:

1478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.00585

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.129

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.123

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.122

AC:

18405

AN:

150258

Hom.:

1480

Cov.:

AF XY:

0.122

AC XY:

8964

AN XY:

73312

show subpopulations

Gnomad4 AFR

AF:

0.0315

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.00587

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.138

Hom.:

222

Bravo

AF:

0.111

Asia WGS

AF:

0.0670

AC:

232

AN:

3478

ClinVar

Significance: Uncertain significance; association

Submissions summary: Uncertain:3Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Susceptibility to severe coronavirus disease (COVID-19)

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 13, 2024

The NC_000011.10:g.1291476C>G (rs111521887) is an intron variant in TOLLIP (toll interacting protein) that has been associated with idiopathic pulmonary fibrosis and other lung diseases. We evaluated this variant in 923 patients with COVID-19 and we did not find any association with mortality or severity risk. Due to the lack of association of the variant with the studied phenotypes, it was classified as uncertain significance. -

Chronic obstructive pulmonary disease

Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 04, 2021

- -

Combined pulmonary fibrosis-emphysema syndrome

Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 04, 2021

- -

Interstitial lung disease 2

Other:1

association, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.47

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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