rs5743987

chr11-1284616-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.610+1386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,088 control chromosomes in the GnomAD database, including 726 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 0.088 (726 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOLLIP	NM_019009.4	c.610+1386G>A		intron_variant		ENST00000317204.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOLLIP	ENST00000317204.11	c.610+1386G>A		intron_variant		1	NM_019009.4	P1

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13381 AN: 151972 Hom.: 718 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0882 AC: 13412 AN: 152088 Hom.: 726 Cov.: 33 AF XY: 0.0865 AC XY: 6429 AN XY: 74330

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0986

Gnomad4 EAS AF: 0.00310

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.0770

Gnomad4 NFE AF: 0.0627

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0802 Hom.: 65

Bravo AF: 0.0887

Asia WGS AF: 0.0460 AC: 160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.4
Dann	Benign	0.25

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: rs5743987; hg19: chr11-1305846;