chr11-1304599-T-C

Position:

• chr11-1304599-T-C

Variant summary

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

The NM_019009.4(TOLLIP):​c.33+4867A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 152,302 control chromosomes in the GnomAD database, including 938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.096 (938 hom., cov: 32)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:2
• Conservation: PhyloP100: -1.27

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.33+4867A>G		intron_variant		ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.33+4867A>G		intron_variant		1	NM_019009.4	ENSP00000314733	P1

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14635 AN: 152184 Hom.: 937 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0952

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0961 AC: 14636 AN: 152302 Hom.: 938 Cov.: 32 AF XY: 0.0923 AC XY: 6871 AN XY: 74478

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.0951

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.0967

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.113

Alfa AF: 0.137 Hom.: 1421

Bravo AF: 0.0929

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: no assertion criteria provided

Submissions by phenotype

Interstitial lung disease 2 Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 04, 2021

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.64

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: rs5743890; hg19: chr11-1325829;