11-1292679-C-T

Variant names:

• chr11-1292679-C-T
• rs5743944
• NM_019009.4:c.184-2270G>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.184-2270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,256 control chromosomes in the GnomAD database, including 2,785 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 0.17 (2785 hom., cov: 34)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.184-2270G>A		intron_variant	Intron 2 of 5	ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.184-2270G>A		intron_variant	Intron 2 of 5	1	NM_019009.4	ENSP00000314733.5

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26127 AN: 152138 Hom.: 2778 Cov.: 34

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.172 AC: 26144 AN: 152256 Hom.: 2785 Cov.: 34 AF XY: 0.168 AC XY: 12521 AN XY: 74442

African (AFR) AF: 0.0474 AC: 1969 AN: 41564

American (AMR) AF: 0.226 AC: 3457 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1193 AN: 5178

South Asian (SAS) AF: 0.148 AC: 712 AN: 4826

European-Finnish (FIN) AF: 0.138 AC: 1468 AN: 10604

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15798 AN: 68008

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.0937 Hom.: 150

Bravo AF: 0.174

Asia WGS AF: 0.218 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		-0.46
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: rs5743944; hg19: chr11-1313909;