dbSNP rs8782: TLE1:p.Thr563Thr (chr9-81590945-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

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

The NM_005077.5(TLE1):c.1689C>T(p.Thr563Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,614,102 control chromosomes in the GnomAD database, including 83,193 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 0.26 ( 5829 hom., cov: 33)

Exomes 𝑓: 0.32 ( 77364 hom. )

Consequence

TLE1
NM_005077.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Publications

17 publications found

Variant links:

Genes affected

TLE1 (HGNC:11837): (TLE family member 1, transcriptional corepressor) Enables identical protein binding activity and transcription corepressor activity. Involved in negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of anoikis; and regulation of gene expression. Located in cytosol and nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

TLE1 Gene-Disease associations (from GenCC):

movement disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

TLE1 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=-0.42).

BP7

Synonymous conserved (PhyloP=1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE1	NM_005077.5 link	c.1689C>T	p.Thr563Thr	synonymous_variant	Exon 16 of 20	ENST00000376499.8	NP_005068.2	Q04724Q59EF7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE1	ENST00000376499.8 link	c.1689C>T	p.Thr563Thr	synonymous_variant	Exon 16 of 20	1	NM_005077.5	ENSP00000365682.3		Q04724

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39569

AN:

152110

Hom.:

5828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.0519

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.302

GnomAD2 exomes

AF:

0.254

AC:

63873

AN:

251422

AF XY:

0.260

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.0455

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.339

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.316

AC:

462581

AN:

1461874

Hom.:

77364

Cov.:

AF XY:

0.315

AC XY:

228807

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.171

AC:

5736

AN:

33480

American (AMR)

AF:

0.165

AC:

7399

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

10319

AN:

26136

East Asian (EAS)

AF:

0.0531

AC:

2110

AN:

39700

South Asian (SAS)

AF:

0.197

AC:

16956

AN:

86256

European-Finnish (FIN)

AF:

0.218

AC:

11658

AN:

53416

Middle Eastern (MID)

AF:

0.418

AC:

2411

AN:

5766

European-Non Finnish (NFE)

AF:

0.348

AC:

387059

AN:

1112002

Other (OTH)

AF:

0.313

AC:

18933

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

22976

45953

68929

91906

114882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12164

24328

36492

48656

60820

<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:

0.260

AC:

39571

AN:

152228

Hom.:

5829

Cov.:

AF XY:

0.250

AC XY:

18597

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.170

AC:

7069

AN:

41548

American (AMR)

AF:

0.217

AC:

3314

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1414

AN:

3470

East Asian (EAS)

AF:

0.0522

AC:

270

AN:

5176

South Asian (SAS)

AF:

0.182

AC:

881

AN:

4832

European-Finnish (FIN)

AF:

0.218

AC:

2314

AN:

10594

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23124

AN:

67992

Other (OTH)

AF:

0.298

AC:

629

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1497

2993

4490

5986

7483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.308

Hom.:

3495

Bravo

AF:

0.260

Asia WGS

AF:

0.125

AC:

437

AN:

3478

EpiCase

AF:

0.351

EpiControl

AF:

0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.8

(source)

DANN

Benign

0.59

PhyloP100

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over