rs5743947

Variant names:

• chr11-1292434-C-T
• rs5743947
• NM_019009.4:c.184-2025G>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.184-2025G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 152,294 control chromosomes in the GnomAD database, including 337 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 0.023 (337 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.184-2025G>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.184-2025G>A		intron_variant	Intron 2 of 5	1	NM_019009.4	ENSP00000314733.5

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3563 AN: 152176 Hom.: 338 Cov.: 33

Gnomad AFR AF: 0.00705

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0234 AC: 3561 AN: 152294 Hom.: 337 Cov.: 33 AF XY: 0.0279 AC XY: 2079 AN XY: 74486

African (AFR) AF: 0.00703 AC: 292 AN: 41562

American (AMR) AF: 0.0672 AC: 1028 AN: 15292

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

East Asian (EAS) AF: 0.289 AC: 1497 AN: 5174

South Asian (SAS) AF: 0.122 AC: 588 AN: 4826

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 68032

Other (OTH) AF: 0.0227 AC: 48 AN: 2110

Alfa AF: 0.0109 Hom.: 15

Bravo AF: 0.0292

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-0.96
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: rs5743947; hg19: chr11-1313664;