NM_005077.5:c.1331+2905C>T

Variant names:

• chr9-81607315-G-A
• rs10867778
• NM_005077.5:c.1331+2905C>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+2905C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 149,672 control chromosomes in the GnomAD database, including 4,238 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 0.19 (4238 hom., cov: 31)
• Consequence: TLE1 NM_005077.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE1	NM_005077.5	MANE Select	c.1331+2905C>T		intron	N/A	NP_005068.2
	TLE1	NM_001303103.2		c.1361+2905C>T		intron	N/A	NP_001290032.1
	TLE1	NM_001303104.2		c.1286+2905C>T		intron	N/A	NP_001290033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE1	ENST00000376499.8	TSL:1 MANE Select	c.1331+2905C>T		intron	N/A	ENSP00000365682.3
	TLE1	ENST00000376484.2	TSL:3	c.413+2905C>T		intron	N/A	ENSP00000365667.2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 27876 AN: 149558 Hom.: 4239 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.0442

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0769

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.186 AC: 27902 AN: 149672 Hom.: 4238 Cov.: 31 AF XY: 0.192 AC XY: 14032 AN XY: 72984

African (AFR) AF: 0.371 AC: 15145 AN: 40774

American (AMR) AF: 0.190 AC: 2821 AN: 14842

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 255 AN: 3448

East Asian (EAS) AF: 0.570 AC: 2915 AN: 5118

South Asian (SAS) AF: 0.181 AC: 857 AN: 4728

European-Finnish (FIN) AF: 0.138 AC: 1409 AN: 10204

Middle Eastern (MID) AF: 0.0833 AC: 24 AN: 288

European-Non Finnish (NFE) AF: 0.0608 AC: 4097 AN: 67336

Other (OTH) AF: 0.167 AC: 339 AN: 2030

Alfa AF: 0.102 Hom.: 7208

Bravo AF: 0.198

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.053
DANN	Benign	0.21
PhyloP100		-0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs10867778; hg19: chr9-84222230;