Menu
GeneBe

9-79720246-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007005.6(TLE4):c.1791C>T(p.Ser597=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000594 in 1,614,086 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 4 hom. )

Consequence

TLE4
NM_007005.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.96
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-79720246-C-T is Benign according to our data. Variant chr9-79720246-C-T is described in ClinVar as [Benign]. Clinvar id is 716982.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.96 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 334 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLE4NM_007005.6 linkuse as main transcriptc.1791C>T p.Ser597= synonymous_variant 16/20 ENST00000376552.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLE4ENST00000376552.8 linkuse as main transcriptc.1791C>T p.Ser597= synonymous_variant 16/201 NM_007005.6 P1Q04727-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00220
AC:
334
AN:
152124
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00717
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000967
AC:
243
AN:
251390
Hom.:
0
AF XY:
0.000957
AC XY:
130
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.00843
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00134
Gnomad FIN exome
AF:
0.000324
Gnomad NFE exome
AF:
0.000449
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000422
AC:
617
AN:
1461844
Hom.:
4
Cov.:
31
AF XY:
0.000421
AC XY:
306
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00857
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00122
Gnomad4 FIN exome
AF:
0.000225
Gnomad4 NFE exome
AF:
0.000127
Gnomad4 OTH exome
AF:
0.000679
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00225
AC:
342
AN:
152242
Hom.:
2
Cov.:
32
AF XY:
0.00224
AC XY:
167
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.00734
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000984
Hom.:
0
Bravo
AF:
0.00240
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
0.41
Dann
Benign
0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61112339; hg19: chr9-82335161; COSMIC: COSV54641945; COSMIC: COSV54641945; API