rs5744034

Variant names:

• chr11-1275007-A-G
• rs5744034
• NM_019009.4:c.*2032T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 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.*2032T>C		3_prime_UTR	Exon 6 of 6	NP_061882.2
	TOLLIP	NM_001318512.2		c.*2032T>C		3_prime_UTR	Exon 5 of 5	NP_001305441.1	B3KR28
	TOLLIP	NM_001318516.2		c.*2032T>C		3_prime_UTR	Exon 5 of 5	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.*2032T>C		3_prime_UTR	Exon 6 of 6	ENSP00000314733.5	Q9H0E2-1
	TOLLIP	ENST00000961564.1		c.*2032T>C		3_prime_UTR	Exon 7 of 7	ENSP00000631623.1
	TOLLIP	ENST00000525159.5	TSL:2	c.*2032T>C		3_prime_UTR	Exon 5 of 5	ENSP00000432668.1	F2Z2Y8

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0331 AC: 1376 AN: 41584

American (AMR) AF: 0.110 AC: 1681 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3472

East Asian (EAS) AF: 0.00717 AC: 37 AN: 5162

South Asian (SAS) AF: 0.137 AC: 659 AN: 4820

European-Finnish (FIN) AF: 0.206 AC: 2189 AN: 10616

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12308 AN: 68000

Other (OTH) AF: 0.128 AC: 271 AN: 2114

Alfa AF: 0.157 Hom.: 8020

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		0.78
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: rs5744034; hg19: chr11-1296237; COSMIC: COSV55137677; COSMIC: COSV55137677;