rs3793964

Variant names:

• chr11-1280752-T-C
• rs3793964
• NM_019009.4:c.611-3499A>G

Variant summary

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

The NM_019009.4(TOLLIP):​c.611-3499A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,660 control chromosomes in the GnomAD database, including 32,606 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 0.65 (32606 hom., cov: 30)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 21 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019009.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP	NM_019009.4	MANE Select	c.611-3499A>G		intron	N/A	NP_061882.2
	TOLLIP	NM_001318512.2		c.461-3499A>G		intron	N/A	NP_001305441.1	B3KR28
	TOLLIP	NM_001318516.2		c.428-3499A>G		intron	N/A	NP_001305445.1	F2Z2Y8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP	ENST00000317204.11	TSL:1 MANE Select	c.611-3499A>G		intron	N/A	ENSP00000314733.5	Q9H0E2-1
	TOLLIP	ENST00000863437.1		c.686-3499A>G		intron	N/A	ENSP00000533496.1
	TOLLIP	ENST00000961564.1		c.671-3499A>G		intron	N/A	ENSP00000631623.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98866 AN: 151542 Hom.: 32573 Cov.: 30

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.652 AC: 98946 AN: 151660 Hom.: 32606 Cov.: 30 AF XY: 0.653 AC XY: 48418 AN XY: 74116

African (AFR) AF: 0.730 AC: 30200 AN: 41356

American (AMR) AF: 0.633 AC: 9638 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2158 AN: 3466

East Asian (EAS) AF: 0.395 AC: 2022 AN: 5114

South Asian (SAS) AF: 0.688 AC: 3308 AN: 4808

European-Finnish (FIN) AF: 0.672 AC: 7066 AN: 10522

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42514 AN: 67862

Other (OTH) AF: 0.620 AC: 1306 AN: 2108

Alfa AF: 0.634 Hom.: 40685

Bravo AF: 0.652

Asia WGS AF: 0.497 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.14
PhyloP100		-1.3
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: rs3793964; hg19: chr11-1301982;