chr11-1302334-C-T

Variant names:

• chr11-1302334-C-T
• rs5743899
• NM_019009.4:c.34-6540G>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.34-6540G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,146 control chromosomes in the GnomAD database, including 39,623 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 0.71 (39623 hom., cov: 34)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 41 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.801 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.34-6540G>A		intron	N/A	NP_061882.2
	TOLLIP	NM_001318512.2		c.33+7132G>A		intron	N/A	NP_001305441.1	B3KR28
	TOLLIP	NM_001318516.2		c.34-6540G>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.34-6540G>A		intron	N/A	ENSP00000314733.5	Q9H0E2-1
	TOLLIP	ENST00000863437.1		c.34-6540G>A		intron	N/A	ENSP00000533496.1
	TOLLIP	ENST00000961564.1		c.34-6540G>A		intron	N/A	ENSP00000631623.1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108681 AN: 152028 Hom.: 39613 Cov.: 34

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.715 AC: 108727 AN: 152146 Hom.: 39623 Cov.: 34 AF XY: 0.709 AC XY: 52759 AN XY: 74382

African (AFR) AF: 0.565 AC: 23417 AN: 41472

American (AMR) AF: 0.738 AC: 11300 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2788 AN: 3472

East Asian (EAS) AF: 0.617 AC: 3190 AN: 5166

South Asian (SAS) AF: 0.733 AC: 3533 AN: 4822

European-Finnish (FIN) AF: 0.679 AC: 7185 AN: 10582

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54844 AN: 68014

Other (OTH) AF: 0.738 AC: 1559 AN: 2112

Alfa AF: 0.773 Hom.: 119686

Bravo AF: 0.712

Asia WGS AF: 0.658 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.88
PhyloP100		-0.36
PromoterAI		-0.061	Neutral
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: rs5743899; hg19: chr11-1323564;