11-1291476-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Uncertain significance; association no assertion criteria provided U:2 O:1
• Conservation: PhyloP100: 0.0880

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]

ACMG classification

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	UniProt
TOLLIP	NM_019009.4	c.184-1067G>C		intron_variant		ENST00000317204.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOLLIP	ENST00000317204.11	c.184-1067G>C		intron_variant		1	NM_019009.4	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18402 AN: 150142 Hom.: 1478 Cov.: 24

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.: 24 AF XY: 0.122 AC XY: 8964 AN XY: 73312

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:2 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Other links and lift over

dbSNP: rs111521887; hg19: chr11-1312706; COSMIC: COSV55138453; COSMIC: COSV55138453;