9-81598245-C-T

Variant names:

• chr9-81598245-C-T
• rs2777777
• NM_005077.5:c.1332-4971G>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.1332-4971G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,902 control chromosomes in the GnomAD database, including 15,220 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 0.44 (15220 hom., cov: 31)
• Consequence: TLE1 NM_005077.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31
• Publications: 7 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 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.1332-4971G>A		intron	N/A	NP_005068.2
	TLE1	NM_001303103.2		c.1362-4971G>A		intron	N/A	NP_001290032.1
	TLE1	NM_001303104.2		c.1287-4971G>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.1332-4971G>A		intron	N/A	ENSP00000365682.3	Q04724
	TLE1	ENST00000946444.1		c.1467-4971G>A		intron	N/A	ENSP00000616503.1
	TLE1	ENST00000946428.1		c.1434-4971G>A		intron	N/A	ENSP00000616487.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66850 AN: 151784 Hom.: 15183 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0701

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.441 AC: 66938 AN: 151902 Hom.: 15220 Cov.: 31 AF XY: 0.438 AC XY: 32516 AN XY: 74258

African (AFR) AF: 0.495 AC: 20476 AN: 41382

American (AMR) AF: 0.393 AC: 5995 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1382 AN: 3468

East Asian (EAS) AF: 0.0707 AC: 365 AN: 5166

South Asian (SAS) AF: 0.349 AC: 1684 AN: 4826

European-Finnish (FIN) AF: 0.474 AC: 4999 AN: 10544

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30560 AN: 67926

Other (OTH) AF: 0.452 AC: 955 AN: 2112

Alfa AF: 0.435 Hom.: 22771

Bravo AF: 0.438

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.053
DANN	Benign	0.52
PhyloP100		-3.3
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: rs2777777; hg19: chr9-84213160;