rs5743987

Variant names:

• chr11-1284616-C-T
• rs5743987
• NM_019009.4:c.610+1386G>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.610+1386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,088 control chromosomes in the GnomAD database, including 726 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 0.088 (726 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.159 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.610+1386G>A		intron	N/A	NP_061882.2
	TOLLIP	NM_001318512.2		c.460+1386G>A		intron	N/A	NP_001305441.1	B3KR28
	TOLLIP	NM_001318516.2		c.427+1386G>A		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.610+1386G>A		intron	N/A	ENSP00000314733.5	Q9H0E2-1
	TOLLIP	ENST00000863437.1		c.685+1386G>A		intron	N/A	ENSP00000533496.1
	TOLLIP	ENST00000961564.1		c.670+1386G>A		intron	N/A	ENSP00000631623.1

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13381 AN: 151972 Hom.: 718 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0882 AC: 13412 AN: 152088 Hom.: 726 Cov.: 33 AF XY: 0.0865 AC XY: 6429 AN XY: 74330

African (AFR) AF: 0.162 AC: 6721 AN: 41462

American (AMR) AF: 0.0455 AC: 695 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0986 AC: 342 AN: 3468

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5156

South Asian (SAS) AF: 0.0731 AC: 352 AN: 4816

European-Finnish (FIN) AF: 0.0770 AC: 816 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0627 AC: 4261 AN: 67986

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0825 Hom.: 71

Bravo AF: 0.0887

Asia WGS AF: 0.0460 AC: 160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.25
PhyloP100		-1.2
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: rs5743987; hg19: chr11-1305846;