rs5743859

Positions:

• chr11-1308045-G-A
• chr11-1308045-G-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+1421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,212 control chromosomes in the GnomAD database, including 1,780 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 0.14 (1780 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOLLIP	NM_019009.4	c.33+1421C>T		intron_variant		ENST00000317204.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOLLIP	ENST00000317204.11	c.33+1421C>T		intron_variant		1	NM_019009.4	P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20795 AN: 152092 Hom.: 1779 Cov.: 33

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.137 AC: 20797 AN: 152212 Hom.: 1780 Cov.: 33 AF XY: 0.131 AC XY: 9766 AN XY: 74430

Gnomad4 AFR AF: 0.0579

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0778

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.158

Alfa AF: 0.0940 Hom.: 140

Bravo AF: 0.132

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.82

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: rs5743859; hg19: chr11-1329275;