rs8782

Variant names:

• chr9-81590945-G-A
• rs8782
• NM_005077.5:c.1689C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005077.5(TLE1):​c.1689C>T​(p.Thr563Thr) 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
• Publications: 17 publications found

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]

TLE1 Gene-Disease associations (from GenCC):

• movement disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005077.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE1	NM_005077.5	MANE Select	c.1689C>T	p.Thr563Thr	synonymous	Exon 16 of 20	NP_005068.2
	TLE1	NM_001303103.2		c.1719C>T	p.Thr573Thr	synonymous	Exon 16 of 20	NP_001290032.1
	TLE1	NM_001303104.2		c.1644C>T	p.Thr548Thr	synonymous	Exon 16 of 20	NP_001290033.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE1	ENST00000376499.8	TSL:1 MANE Select	c.1689C>T	p.Thr563Thr	synonymous	Exon 16 of 20	ENSP00000365682.3	Q04724
	TLE1	ENST00000946444.1		c.1824C>T	p.Thr608Thr	synonymous	Exon 17 of 21	ENSP00000616503.1
	TLE1	ENST00000946428.1		c.1791C>T	p.Thr597Thr	synonymous	Exon 17 of 21	ENSP00000616487.1

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

GnomAD2 exomes AF: 0.254 AC: 63873 AN: 251422 AF XY: 0.260

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 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

African (AFR) AF: 0.171 AC: 5736 AN: 33480

American (AMR) AF: 0.165 AC: 7399 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 10319 AN: 26136

East Asian (EAS) AF: 0.0531 AC: 2110 AN: 39700

South Asian (SAS) AF: 0.197 AC: 16956 AN: 86256

European-Finnish (FIN) AF: 0.218 AC: 11658 AN: 53416

Middle Eastern (MID) AF: 0.418 AC: 2411 AN: 5766

European-Non Finnish (NFE) AF: 0.348 AC: 387059 AN: 1112002

Other (OTH) AF: 0.313 AC: 18933 AN: 60396

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

African (AFR) AF: 0.170 AC: 7069 AN: 41548

American (AMR) AF: 0.217 AC: 3314 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1414 AN: 3470

East Asian (EAS) AF: 0.0522 AC: 270 AN: 5176

South Asian (SAS) AF: 0.182 AC: 881 AN: 4832

European-Finnish (FIN) AF: 0.218 AC: 2314 AN: 10594

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23124 AN: 67992

Other (OTH) AF: 0.298 AC: 629 AN: 2114

Alfa AF: 0.308 Hom.: 3495

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.8
DANN	Benign	0.59
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

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