11-1279176-C-T

Position:

• chr11-1279176-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019009.4(TOLLIP):​c.611-1923G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,144 control chromosomes in the GnomAD database, including 18,247 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 0.49 (18247 hom., cov: 33)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.611-1923G>A		intron_variant		ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.611-1923G>A		intron_variant		1	NM_019009.4	ENSP00000314733.5

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74166 AN: 152026 Hom.: 18240 Cov.: 33

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.488 AC: 74202 AN: 152144 Hom.: 18247 Cov.: 33 AF XY: 0.486 AC XY: 36181 AN XY: 74380

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.463

Alfa AF: 0.497 Hom.: 29848

Bravo AF: 0.488

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.70

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: rs3829223; hg19: chr11-1300406;