11-1307121-G-A

Position:

• chr11-1307121-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.33+2345C>T		intron_variant		ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.33+2345C>T		intron_variant		1	NM_019009.4	ENSP00000314733	P1

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

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.895

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.868

Alfa AF: 0.914 Hom.: 73262

Bravo AF: 0.865

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743867; hg19: chr11-1328351;