9-81597507-A-T

Position:

• chr9-81597507-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLE1	NM_005077.5	c.1332-4233T>A		intron_variant		ENST00000376499.8	NP_005068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLE1	ENST00000376499.8	c.1332-4233T>A		intron_variant		1	NM_005077.5	ENSP00000365682.3

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

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.0704

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.451

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.39
DANN	Benign	0.73

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: rs1539377; hg19: chr9-84212422;