rs5743856

Positions:

• chr11-1308608-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+858A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 152,348 control chromosomes in the GnomAD database, including 215 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 0.046 (215 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.33+858A>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+858A>G		intron_variant		1	NM_019009.4	ENSP00000314733	P1

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7027 AN: 152230 Hom.: 214 Cov.: 33

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.00829

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0430

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

GnomAD4 genome AF: 0.0462 AC: 7036 AN: 152348 Hom.: 215 Cov.: 33 AF XY: 0.0448 AC XY: 3339 AN XY: 74498

Gnomad4 AFR AF: 0.0889

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0819

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.0623

Gnomad4 FIN AF: 0.00829

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0391 Hom.: 20

Bravo AF: 0.0494

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.71

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: rs5743856; hg19: chr11-1329838;