9-81597507-A-T

Variant names:

• chr9-81597507-A-T
• rs1539377
• NM_005077.5:c.1332-4233T>A

Variant summary

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

The NM_005077.5(TLE1):​c.1332-4233T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,922 control chromosomes in the GnomAD database, including 14,751 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 0.43 (14751 hom., cov: 31)
• Consequence: TLE1 NM_005077.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 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.1332-4233T>A		intron	N/A	NP_005068.2
	TLE1	NM_001303103.2		c.1362-4233T>A		intron	N/A	NP_001290032.1
	TLE1	NM_001303104.2		c.1287-4233T>A		intron	N/A	NP_001290033.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE1	ENST00000376499.8	TSL:1 MANE Select	c.1332-4233T>A		intron	N/A	ENSP00000365682.3	Q04724
	TLE1	ENST00000946444.1		c.1467-4233T>A		intron	N/A	ENSP00000616503.1
	TLE1	ENST00000946428.1		c.1434-4233T>A		intron	N/A	ENSP00000616487.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65908 AN: 151802 Hom.: 14715 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.0699

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.434 AC: 65996 AN: 151922 Hom.: 14751 Cov.: 31 AF XY: 0.432 AC XY: 32049 AN XY: 74200

African (AFR) AF: 0.472 AC: 19543 AN: 41408

American (AMR) AF: 0.391 AC: 5966 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1373 AN: 3472

East Asian (EAS) AF: 0.0704 AC: 364 AN: 5170

South Asian (SAS) AF: 0.351 AC: 1688 AN: 4808

European-Finnish (FIN) AF: 0.473 AC: 4983 AN: 10524

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30606 AN: 67954

Other (OTH) AF: 0.451 AC: 952 AN: 2112

Alfa AF: 0.317 Hom.: 804

Bravo AF: 0.431

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.39
DANN	Benign	0.73
PhyloP100		-1.1
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: rs1539377; hg19: chr9-84212422;