11-1307121-G-A

Variant names:

• chr11-1307121-G-A
• rs5743867
• NM_019009.4:c.33+2345C>T

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+2345C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,168 control chromosomes in the GnomAD database, including 57,083 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 0.86 (57083 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 26 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP	NM_019009.4	MANE Select	c.33+2345C>T		intron	N/A	NP_061882.2
	TOLLIP	NM_001318512.2		c.33+2345C>T		intron	N/A	NP_001305441.1
	TOLLIP	NM_001318516.2		c.33+2345C>T		intron	N/A	NP_001305445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP	ENST00000317204.11	TSL:1 MANE Select	c.33+2345C>T		intron	N/A	ENSP00000314733.5
	TOLLIP	ENST00000263646.11	TSL:5	c.12+2366C>T		intron	N/A	ENSP00000263646.6
	TOLLIP	ENST00000525159.5	TSL:2	c.33+2345C>T		intron	N/A	ENSP00000432668.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131288 AN: 152052 Hom.: 57067 Cov.: 33

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.863 AC: 131357 AN: 152168 Hom.: 57083 Cov.: 33 AF XY: 0.857 AC XY: 63781 AN XY: 74386

African (AFR) AF: 0.786 AC: 32602 AN: 41476

American (AMR) AF: 0.895 AC: 13704 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3284 AN: 3472

East Asian (EAS) AF: 0.622 AC: 3212 AN: 5164

South Asian (SAS) AF: 0.856 AC: 4131 AN: 4826

European-Finnish (FIN) AF: 0.826 AC: 8741 AN: 10586

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62820 AN: 68018

Other (OTH) AF: 0.868 AC: 1836 AN: 2116

Alfa AF: 0.903 Hom.: 218266

Bravo AF: 0.865

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.61
PhyloP100		-0.88
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: rs5743867; hg19: chr11-1328351;