chr9-81598245-C-T

Position:

• chr9-81598245-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005077.5(TLE1):​c.1332-4971G>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

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLE1	NM_005077.5	c.1332-4971G>A		intron_variant		ENST00000376499.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLE1	ENST00000376499.8	c.1332-4971G>A		intron_variant		1	NM_005077.5	P1

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

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.0707

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.452

Alfa AF: 0.421 Hom.: 11081

Bravo AF: 0.438

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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