Genetic Variant TOLLIP:p.Pro139Pro (chr11-1288726-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_019009.4(TOLLIP):c.417G>A(p.Pro139Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,612,456 control chromosomes in the GnomAD database, including 143,899 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 0.38 ( 11315 hom., cov: 33)

Exomes 𝑓: 0.42 ( 132584 hom. )

Consequence

TOLLIP
NM_019009.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

103 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=-1.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOLLIP	NM_019009.4 link	c.417G>A	p.Pro139Pro	synonymous_variant	Exon 4 of 6	ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11 link	c.417G>A	p.Pro139Pro	synonymous_variant	Exon 4 of 6	1	NM_019009.4	ENSP00000314733.5

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57748

AN:

152030

Hom.:

11311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.387

GnomAD2 exomes

AF:

0.396

AC:

98817

AN:

249664

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.435

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.423

AC:

618380

AN:

1460308

Hom.:

132584

Cov.:

AF XY:

0.425

AC XY:

308406

AN XY:

726456

show subpopulations

African (AFR)

AF:

0.293

AC:

9808

AN:

33474

American (AMR)

AF:

0.347

AC:

15523

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

9983

AN:

26118

East Asian (EAS)

AF:

0.272

AC:

10802

AN:

39692

South Asian (SAS)

AF:

0.428

AC:

36920

AN:

86222

European-Finnish (FIN)

AF:

0.394

AC:

20607

AN:

52330

Middle Eastern (MID)

AF:

0.417

AC:

2404

AN:

5762

European-Non Finnish (NFE)

AF:

0.438

AC:

487136

AN:

1111692

Other (OTH)

AF:

0.418

AC:

25197

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

19894

39788

59683

79577

99471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14606

29212

43818

58424

73030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.380

AC:

57758

AN:

152148

Hom.:

11315

Cov.:

AF XY:

0.376

AC XY:

28006

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.293

AC:

12173

AN:

41500

American (AMR)

AF:

0.361

AC:

5525

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

1286

AN:

3472

East Asian (EAS)

AF:

0.305

AC:

1579

AN:

5172

South Asian (SAS)

AF:

0.428

AC:

2069

AN:

4830

European-Finnish (FIN)

AF:

0.380

AC:

4026

AN:

10590

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29855

AN:

67980

Other (OTH)

AF:

0.385

AC:

811

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1896

3792

5687

7583

9479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.416

Hom.:

27149

Bravo

AF:

0.374

Asia WGS

AF:

0.342

AC:

1192

AN:

3478

EpiCase

AF:

0.434

EpiControl

AF:

0.440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.11

(source)

DANN

Benign

0.70

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over