Genetic Variant NM_007005.6:c.592+23C>G (chr9-79652817-C-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_007005.6(TLE4):c.592+23C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 1,610,218 control chromosomes in the GnomAD database, including 311,933 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 0.53 ( 23743 hom., cov: 32)

Exomes 𝑓: 0.62 ( 288190 hom. )

Consequence

TLE4
NM_007005.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11

Publications

11 publications found

Variant links:

Genes affected

TLE4 (HGNC:11840): (TLE family member 4, transcriptional corepressor) Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway. Predicted to act upstream of or within Wnt signaling pathway; cellular response to leukemia inhibitory factor; and negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

TLE4 links:

Genome browser will be placed here

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=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE4	NM_007005.6 link	c.592+23C>G		intron_variant	Intron 7 of 19	ENST00000376552.8	NP_008936.2	Q04727-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE4	ENST00000376552.8 link	c.592+23C>G		intron_variant	Intron 7 of 19	1	NM_007005.6	ENSP00000365735.2		Q04727-1

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80731

AN:

151930

Hom.:

23730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.611

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.734

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.651

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.546

GnomAD2 exomes

AF:

0.625

AC:

155691

AN:

249080

AF XY:

0.631

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.676

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.735

Gnomad FIN exome

AF:

0.639

Gnomad NFE exome

AF:

0.627

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

AF:

0.625

AC:

911063

AN:

1458170

Hom.:

288190

Cov.:

AF XY:

0.628

AC XY:

455379

AN XY:

725676

show subpopulations

African (AFR)

AF:

0.258

AC:

8627

AN:

33386

American (AMR)

AF:

0.667

AC:

29807

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

14663

AN:

26108

East Asian (EAS)

AF:

0.707

AC:

28042

AN:

39672

South Asian (SAS)

AF:

0.693

AC:

59612

AN:

85992

European-Finnish (FIN)

AF:

0.640

AC:

34061

AN:

53250

Middle Eastern (MID)

AF:

0.630

AC:

3629

AN:

5760

European-Non Finnish (NFE)

AF:

0.627

AC:

695629

AN:

1109062

Other (OTH)

AF:

0.614

AC:

36993

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

18173

36346

54520

72693

90866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18468

36936

55404

73872

92340

<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:

0.531

AC:

80751

AN:

152048

Hom.:

23743

Cov.:

AF XY:

0.535

AC XY:

39784

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.263

AC:

10894

AN:

41474

American (AMR)

AF:

0.606

AC:

9255

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1958

AN:

3472

East Asian (EAS)

AF:

0.734

AC:

3784

AN:

5154

South Asian (SAS)

AF:

0.698

AC:

3361

AN:

4818

European-Finnish (FIN)

AF:

0.651

AC:

6873

AN:

10560

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.629

AC:

42721

AN:

67968

Other (OTH)

AF:

0.551

AC:

1163

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1734

3467

5201

6934

8668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.523

Hom.:

3081

Bravo

AF:

0.512

Asia WGS

AF:

0.685

AC:

2382

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.0

(source)

DANN

Benign

0.77

PhyloP100

2.1

PromoterAI

0.024

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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