9-81607703-G-A

Variant names:

• chr9-81607703-G-A
• rs815847
• NM_005077.5:c.1331+2517C>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.1331+2517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,966 control chromosomes in the GnomAD database, including 29,296 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 0.61 (29296 hom., cov: 33)
• Consequence: TLE1 NM_005077.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE1	NM_005077.5	c.1331+2517C>T		intron_variant	Intron 14 of 19	ENST00000376499.8	NP_005068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE1	ENST00000376499.8	c.1331+2517C>T		intron_variant	Intron 14 of 19	1	NM_005077.5	ENSP00000365682.3
TLE1	ENST00000376484.2	c.413+2517C>T		intron_variant	Intron 3 of 3	3		ENSP00000365667.2

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93394 AN: 151848 Hom.: 29288 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.615 AC: 93458 AN: 151966 Hom.: 29296 Cov.: 33 AF XY: 0.611 AC XY: 45417 AN XY: 74284

African (AFR) AF: 0.605 AC: 25089 AN: 41450

American (AMR) AF: 0.565 AC: 8627 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2594 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1043 AN: 5110

South Asian (SAS) AF: 0.510 AC: 2454 AN: 4814

European-Finnish (FIN) AF: 0.653 AC: 6913 AN: 10580

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.655 AC: 44549 AN: 67964

Other (OTH) AF: 0.643 AC: 1356 AN: 2108

Alfa AF: 0.639 Hom.: 105114

Bravo AF: 0.606

Asia WGS AF: 0.412 AC: 1431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.32
PhyloP100		-0.84
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: rs815847; hg19: chr9-84222618;