rs5744034

Positions:

• chr11-1275007-A-G
• chr11-1275007-A-T

Variant summary

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

The NM_019009.4(TOLLIP):​c.*2032T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,280 control chromosomes in the GnomAD database, including 1,556 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 0.13 (1556 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TOLLIP NM_019009.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778

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 = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOLLIP	NM_019009.4	c.*2032T>C		3_prime_UTR_variant	6/6	ENST00000317204.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOLLIP	ENST00000317204.11	c.*2032T>C		3_prime_UTR_variant	6/6	1	NM_019009.4	P1
TOLLIP	ENST00000525159.5	c.*2032T>C		3_prime_UTR_variant	5/5	2
TOLLIP	ENST00000527886.5	c.*2032T>C		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19235 AN: 152162 Hom.: 1554 Cov.: 33

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00715

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.127

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.126 AC: 19238 AN: 152280 Hom.: 1556 Cov.: 33 AF XY: 0.127 AC XY: 9439 AN XY: 74476

Gnomad4 AFR AF: 0.0331

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.00717

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.128

Alfa AF: 0.163 Hom.: 3689

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.46

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: rs5744034; hg19: chr11-1296237; COSMIC: COSV55137677; COSMIC: COSV55137677;