rs6559629

Variant names:

• chr9-81592445-G-A
• rs6559629
• NM_005077.5:c.1581+580C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005077.5(TLE1):​c.1581+580C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,020 control chromosomes in the GnomAD database, including 20,552 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 0.52 (20552 hom., cov: 33)
• Consequence: TLE1 NM_005077.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE1	NM_005077.5	c.1581+580C>T		intron_variant	Intron 15 of 19	ENST00000376499.8	NP_005068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE1	ENST00000376499.8	c.1581+580C>T		intron_variant	Intron 15 of 19	1	NM_005077.5	ENSP00000365682.3

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78443 AN: 151902 Hom.: 20544 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.470

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.516 AC: 78480 AN: 152020 Hom.: 20552 Cov.: 33 AF XY: 0.525 AC XY: 38985 AN XY: 74298

African (AFR) AF: 0.487 AC: 20179 AN: 41456

American (AMR) AF: 0.518 AC: 7910 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3240 AN: 5152

South Asian (SAS) AF: 0.693 AC: 3333 AN: 4808

European-Finnish (FIN) AF: 0.592 AC: 6264 AN: 10576

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34724 AN: 67964

Other (OTH) AF: 0.468 AC: 989 AN: 2114

Alfa AF: 0.507 Hom.: 28439

Bravo AF: 0.505

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		0.30
Mutation Taster		=100/0	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: rs6559629; hg19: chr9-84207360;