rs10867778

Positions:

• chr9-81607315-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLE1	NM_005077.5	c.1331+2905C>T		intron_variant		ENST00000376499.8	NP_005068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLE1	ENST00000376499.8	c.1331+2905C>T		intron_variant		1	NM_005077.5	ENSP00000365682	P1
TLE1	ENST00000376484.2	c.413+2905C>T		intron_variant		3		ENSP00000365667

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

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.167

Alfa AF: 0.0839 Hom.: 2156

Bravo AF: 0.198

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.053
DANN	Benign	0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs10867778; hg19: chr9-84222230;