9-79652817-C-G

Variant names:

• chr9-79652817-C-G
• rs2297499
• NM_007005.6:c.592+23C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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]

ACMG classification

Verdict is Benign. Variant got -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	c.592+23C>G		intron_variant	Intron 7 of 19	ENST00000376552.8	NP_008936.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80731 AN: 151930 Hom.: 23730 Cov.: 32

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

GnomAD3 exomes AF: 0.625 AC: 155691 AN: 249080 Hom.: 50105 AF XY: 0.631 AC XY: 85285 AN XY: 135122

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 SAS exome AF: 0.694

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.: 31 AF XY: 0.628 AC XY: 455379 AN XY: 725676

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.693

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.614

GnomAD4 genome AF: 0.531 AC: 80751 AN: 152048 Hom.: 23743 Cov.: 32 AF XY: 0.535 AC XY: 39784 AN XY: 74326

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.551

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
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs2297499; hg19: chr9-82267732; COSMIC: COSV54628609; COSMIC: COSV54628609;