Genetic Variant NM_007005.6:c.1026A>T (chr9-79708207-A-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_007005.6(TLE4):c.1026A>T(p.Gly342Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,614,160 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

TLE4
NM_007005.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0150

Publications

2 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.02).

BP6

Variant 9-79708207-A-T is Benign according to our data. Variant chr9-79708207-A-T is described in ClinVar as Benign. ClinVar VariationId is 716285.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.015 with no splicing effect.

BS2

High AC in GnomAd4 at 153 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007005.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLE4	NM_007005.6	MANE Select	c.1026A>T	p.Gly342Gly	synonymous	Exon 12 of 20	NP_008936.2
TLE4	NM_001282748.2		c.1122A>T	p.Gly374Gly	synonymous	Exon 13 of 21	NP_001269677.1	Q04727-3
TLE4	NM_001351541.2		c.1065A>T	p.Gly355Gly	synonymous	Exon 13 of 21	NP_001338470.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLE4	ENST00000376552.8	TSL:1 MANE Select	c.1026A>T	p.Gly342Gly	synonymous	Exon 12 of 20	ENSP00000365735.2	Q04727-1
TLE4	ENST00000376537.8	TSL:1	c.1122A>T	p.Gly374Gly	synonymous	Exon 13 of 21	ENSP00000365720.4	Q04727-3
TLE4	ENST00000376544.7	TSL:1	c.819A>T	p.Gly273Gly	synonymous	Exon 10 of 18	ENSP00000365727.4	Q04727-2

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

153

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00107

AC:

266

AN:

249484

AF XY:

0.00111

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00143

AC:

2095

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1060

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

33480

American (AMR)

AF:

0.000648

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00272

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000505

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00170

AC:

1887

AN:

1112000

Other (OTH)

AF:

0.00103

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

110

220

329

439

549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

152

228

304

380

<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:

0.00100

AC:

153

AN:

152282

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41562

American (AMR)

AF:

0.000980

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00160

AC:

109

AN:

68010

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00187

Hom.:

Bravo

AF:

0.00107

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.6

(source)

DANN

Benign

0.65

PhyloP100

0.015

Mutation Taster

=294/6

polymorphism

(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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over