rs3168046

Positions:

• chr11-1275419-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.*1620C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,840 control chromosomes in the GnomAD database, including 13,572 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 0.42 (13567 hom., cov: 32)
  • Exomes 𝑓: 0.55 (5 hom.)
• Consequence: TOLLIP NM_019009.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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 (SAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.*1620C>T		3_prime_UTR_variant	6/6	ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.*1620C>T		3_prime_UTR_variant	6/6	1	NM_019009.4	ENSP00000314733.5
TOLLIP	ENST00000525159.5	c.*1620C>T		3_prime_UTR_variant	5/5	2		ENSP00000432668.1
TOLLIP	ENST00000527886.5	c.*1620C>T		3_prime_UTR_variant	6/6	2		ENSP00000434035.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63992 AN: 151702 Hom.: 13563 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.550 AC: 11 AN: 20 Hom.: 5 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.688

GnomAD4 genome AF: 0.422 AC: 64016 AN: 151820 Hom.: 13567 Cov.: 32 AF XY: 0.418 AC XY: 31031 AN XY: 74238

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.409

Alfa AF: 0.437 Hom.: 15026

Bravo AF: 0.420

Asia WGS AF: 0.364 AC: 1267 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	0.23
DANN	Benign	0.48

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: rs3168046; hg19: chr11-1296649;