11-1303542-T-C

Variant names:

• chr11-1303542-T-C
• rs5743894
• NM_019009.4:c.33+5924A>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.33+5924A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,244 control chromosomes in the GnomAD database, including 1,543 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 0.13 (1543 hom., cov: 32)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743
• Publications: 41 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.33+5924A>G		intron_variant	Intron 1 of 5	ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.33+5924A>G		intron_variant	Intron 1 of 5	1	NM_019009.4	ENSP00000314733.5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19163 AN: 152126 Hom.: 1541 Cov.: 32

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.126 AC: 19166 AN: 152244 Hom.: 1543 Cov.: 32 AF XY: 0.126 AC XY: 9388 AN XY: 74424

African (AFR) AF: 0.0332 AC: 1378 AN: 41554

American (AMR) AF: 0.110 AC: 1684 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3472

East Asian (EAS) AF: 0.00753 AC: 39 AN: 5176

South Asian (SAS) AF: 0.138 AC: 665 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2170 AN: 10590

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12242 AN: 68004

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.149 Hom.: 3029

Bravo AF: 0.111

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.37
PhyloP100		-0.74
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: rs5743894; hg19: chr11-1324772;