Genetic Variant TOLLIP:c.*2032T>C (chr11-1275007-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.778

Publications

17 publications found

Variant links:

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]

TOLLIP links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
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
TOLLIP	NM_001318516.2		c.*2032T>C	3_prime_UTR	Exon 5 of 5	NP_001305445.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TOLLIP	ENST00000317204.11	TSL:1 MANE Select	c.*2032T>C	3_prime_UTR	Exon 6 of 6	ENSP00000314733.5
TOLLIP	ENST00000525159.5	TSL:2	c.*2032T>C	3_prime_UTR	Exon 5 of 5	ENSP00000432668.1
TOLLIP	ENST00000527886.5	TSL:2	c.*2032T>C	3_prime_UTR	Exon 6 of 6	ENSP00000434035.1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19235

AN:

152162

Hom.:

1554

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.126

AC:

19238

AN:

152280

Hom.:

1556

Cov.:

AF XY:

0.127

AC XY:

9439

AN XY:

74476

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.181

AC:

12308

AN:

68000

Other (OTH)

AF:

0.128

AC:

271

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

892

1783

2675

3566

4458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.46

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over