rs3793963

Variant names:

• chr11-1280678-C-T
• rs3793963
• NM_019009.4:c.611-3425G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019009.4(TOLLIP):​c.611-3425G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 152,074 control chromosomes in the GnomAD database, including 294 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 0.022 (294 hom., cov: 31)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.611-3425G>A		intron_variant	Intron 5 of 5	ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.611-3425G>A		intron_variant	Intron 5 of 5	1	NM_019009.4	ENSP00000314733.5

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3421 AN: 151956 Hom.: 295 Cov.: 31

Gnomad AFR AF: 0.00527

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.00274

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00225

Gnomad OTH AF: 0.0245

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

GnomAD4 genome AF: 0.0225 AC: 3418 AN: 152074 Hom.: 294 Cov.: 31 AF XY: 0.0269 AC XY: 1999 AN XY: 74342

African (AFR) AF: 0.00525 AC: 218 AN: 41504

American (AMR) AF: 0.0675 AC: 1030 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1331 AN: 5140

South Asian (SAS) AF: 0.124 AC: 598 AN: 4818

European-Finnish (FIN) AF: 0.00274 AC: 29 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00225 AC: 153 AN: 67986

Other (OTH) AF: 0.0242 AC: 51 AN: 2104

Alfa AF: 0.0112 Hom.: 14

Bravo AF: 0.0276

Asia WGS AF: 0.155 AC: 541 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	1.2
DANN	Benign	0.76
PhyloP100		-0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3793963; hg19: chr11-1301908;