rs5744002

Positions:

• chr11-1280458-C-T

Variant summary

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

The NM_019009.4(TOLLIP):​c.611-3205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,774 control chromosomes in the GnomAD database, including 25,499 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 0.58 (25499 hom., cov: 31)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.611-3205G>A		intron_variant		ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.611-3205G>A		intron_variant		1	NM_019009.4	ENSP00000314733	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87463 AN: 151656 Hom.: 25475 Cov.: 31

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.577 AC: 87530 AN: 151774 Hom.: 25499 Cov.: 31 AF XY: 0.574 AC XY: 42552 AN XY: 74170

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.545

Alfa AF: 0.553 Hom.: 15820

Bravo AF: 0.578

Asia WGS AF: 0.437 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.075
DANN	Benign	0.69

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: rs5744002; hg19: chr11-1301688;