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GeneBe

9-79722492-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_007005.6(TLE4):c.2028A>C(p.Ala676=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,204 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 29 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 23 hom. )

Consequence

TLE4
NM_007005.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.71
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-79722492-A-C is Benign according to our data. Variant chr9-79722492-A-C is described in ClinVar as [Benign]. Clinvar id is 786910.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=-3.71 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1597/152338) while in subpopulation AFR AF= 0.0357 (1483/41580). AF 95% confidence interval is 0.0342. There are 29 homozygotes in gnomad4. There are 777 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
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 1596 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLE4NM_007005.6 linkuse as main transcriptc.2028A>C p.Ala676= synonymous_variant 18/20 ENST00000376552.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLE4ENST00000376552.8 linkuse as main transcriptc.2028A>C p.Ala676= synonymous_variant 18/201 NM_007005.6 P1Q04727-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0105
AC:
1596
AN:
152220
Hom.:
29
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0357
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00628
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00259
AC:
645
AN:
249456
Hom.:
8
AF XY:
0.00193
AC XY:
261
AN XY:
135366
show subpopulations
Gnomad AFR exome
AF:
0.0368
Gnomad AMR exome
AF:
0.00154
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.00116
GnomAD4 exome
AF:
0.00100
AC:
1469
AN:
1461866
Hom.:
23
Cov.:
31
AF XY:
0.000902
AC XY:
656
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0352
Gnomad4 AMR exome
AF:
0.00228
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000342
Gnomad4 OTH exome
AF:
0.00220
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0105
AC:
1597
AN:
152338
Hom.:
29
Cov.:
33
AF XY:
0.0104
AC XY:
777
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0357
Gnomad4 AMR
AF:
0.00628
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00491
Hom.:
7
Bravo
AF:
0.0122
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

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 testingInvitaeAug 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
0.078
Dann
Benign
0.65

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

LitVar

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

Other links and lift over

dbSNP: rs34566811; hg19: chr9-82337407; API