11-1292798-A-G

Variant names:

• chr11-1292798-A-G
• rs5743942
• NM_019009.4:c.184-2389T>C

Variant summary

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

The NM_019009.4(TOLLIP):​c.184-2389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,170 control chromosomes in the GnomAD database, including 17,874 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 0.48 (17874 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 17 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP	NM_019009.4	MANE Select	c.184-2389T>C		intron	N/A	NP_061882.2
	TOLLIP	NM_001318512.2		c.34-2389T>C		intron	N/A	NP_001305441.1
	TOLLIP	NM_001318516.2		c.183+2847T>C		intron	N/A	NP_001305445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP	ENST00000317204.11	TSL:1 MANE Select	c.184-2389T>C		intron	N/A	ENSP00000314733.5
	TOLLIP	ENST00000263646.11	TSL:5	c.100-2389T>C		intron	N/A	ENSP00000263646.6
	TOLLIP	ENST00000525159.5	TSL:2	c.183+2847T>C		intron	N/A	ENSP00000432668.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72746 AN: 152052 Hom.: 17859 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.478 AC: 72796 AN: 152170 Hom.: 17874 Cov.: 33 AF XY: 0.475 AC XY: 35325 AN XY: 74418

African (AFR) AF: 0.474 AC: 19665 AN: 41514

American (AMR) AF: 0.458 AC: 7013 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3468

East Asian (EAS) AF: 0.0913 AC: 473 AN: 5182

South Asian (SAS) AF: 0.451 AC: 2173 AN: 4818

European-Finnish (FIN) AF: 0.504 AC: 5343 AN: 10596

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34652 AN: 67978

Other (OTH) AF: 0.467 AC: 988 AN: 2114

Alfa AF: 0.502 Hom.: 56688

Bravo AF: 0.475

Asia WGS AF: 0.268 AC: 934 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	0.47
DANN	Benign	0.13
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: rs5743942; hg19: chr11-1314028;