rs8782

Positions:

• chr9-81590945-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005077.5(TLE1):​c.1689C>T​(p.Thr563=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,614,102 control chromosomes in the GnomAD database, including 83,193 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 0.26 (5829 hom., cov: 33)
  • Exomes 𝑓: 0.32 (77364 hom.)
• Consequence: TLE1 NM_005077.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

TLE1 (HGNC:11837): (TLE family member 1, transcriptional corepressor) Enables identical protein binding activity and transcription corepressor activity. Involved in negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of anoikis; and regulation of gene expression. Located in cytosol and nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLE1	NM_005077.5	c.1689C>T	p.Thr563=	synonymous_variant	16/20	ENST00000376499.8	NP_005068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLE1	ENST00000376499.8	c.1689C>T	p.Thr563=	synonymous_variant	16/20	1	NM_005077.5	ENSP00000365682	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39569 AN: 152110 Hom.: 5828 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.302

GnomAD3 exomes AF: 0.254 AC: 63873 AN: 251422 Hom.: 9408 AF XY: 0.260 AC XY: 35325 AN XY: 135894

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.0455

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.291

GnomAD4 exome AF: 0.316 AC: 462581 AN: 1461874 Hom.: 77364 Cov.: 64 AF XY: 0.315 AC XY: 228807 AN XY: 727240

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.395

Gnomad4 EAS exome AF: 0.0531

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.260 AC: 39571 AN: 152228 Hom.: 5829 Cov.: 33 AF XY: 0.250 AC XY: 18597 AN XY: 74426

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.0522

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.298

Alfa AF: 0.310 Hom.: 3481

Bravo AF: 0.260

Asia WGS AF: 0.125 AC: 437 AN: 3478

EpiCase AF: 0.351

EpiControl AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.8
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs8782; hg19: chr9-84205860; COSMIC: COSV64720841;