rs5743890

Variant names:

• chr11-1304599-T-C
• rs5743890
• NM_019009.4:c.33+4867A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-1304599-T-C
• chr11-1304599-T-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.33+4867A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 152,302 control chromosomes in the GnomAD database, including 938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.096 (938 hom., cov: 32)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:2
• Conservation: PhyloP100: -1.27
• Publications: 91 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 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.33+4867A>G		intron	N/A	NP_061882.2
	TOLLIP	NM_001318512.2		c.33+4867A>G		intron	N/A	NP_001305441.1	B3KR28
	TOLLIP	NM_001318516.2		c.33+4867A>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.33+4867A>G		intron	N/A	ENSP00000314733.5	Q9H0E2-1
	TOLLIP	ENST00000863437.1		c.33+4867A>G		intron	N/A	ENSP00000533496.1
	TOLLIP	ENST00000961564.1		c.33+4867A>G		intron	N/A	ENSP00000631623.1

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14635 AN: 152184 Hom.: 937 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0952

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0961 AC: 14636 AN: 152302 Hom.: 938 Cov.: 32 AF XY: 0.0923 AC XY: 6871 AN XY: 74478

African (AFR) AF: 0.0243 AC: 1009 AN: 41566

American (AMR) AF: 0.0951 AC: 1455 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0395 AC: 191 AN: 4830

European-Finnish (FIN) AF: 0.0967 AC: 1026 AN: 10610

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10165 AN: 68014

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.128 Hom.: 3609

Bravo AF: 0.0929

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Chronic obstructive pulmonary disease (1)
-	1	-	Interstitial lung disease 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.64
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: rs5743890; hg19: chr11-1325829;