rs5743942

Positions:

• chr11-1292798-A-G

Variant summary

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

The NM_019009.4(TOLLIP):​c.184-2389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,170 control chromosomes in the GnomAD database, including 17,874 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17874 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOLLIP	NM_019009.4	c.184-2389T>C		intron_variant		ENST00000317204.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOLLIP	ENST00000317204.11	c.184-2389T>C		intron_variant		1	NM_019009.4	P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72746 AN: 152052 Hom.: 17859 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.478 AC: 72796 AN: 152170 Hom.: 17874 Cov.: 33 AF XY: 0.475 AC XY: 35325 AN XY: 74418

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.0913

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.467

Alfa AF: 0.509 Hom.: 24878

Bravo AF: 0.475

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.13

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: rs5743942; hg19: chr11-1314028;