rs216283

chr19-3007700-A-C

Variant summary

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

The NM_003260.5(TLE2):c.1251-1031T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,078 control chromosomes in the GnomAD database, including 32,873 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 0.65 (32873 hom., cov: 33)
• Consequence: TLE2 NM_003260.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

Genes affected

TLE2 (HGNC:11838): (TLE family member 2, transcriptional corepressor) Enables transcription corepressor activity. Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of transcription, DNA-templated. Located in focal adhesion and nuclear body. [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 = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLE2	NM_003260.5	c.1251-1031T>G		intron_variant		ENST00000262953.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLE2	ENST00000262953.11	c.1251-1031T>G		intron_variant		1	NM_003260.5	A1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98383 AN: 151960 Hom.: 32837 Cov.: 33

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.648 AC: 98478 AN: 152078 Hom.: 32873 Cov.: 33 AF XY: 0.642 AC XY: 47735 AN XY: 74346

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.635

Alfa AF: 0.599 Hom.: 15812

Bravo AF: 0.664

Asia WGS AF: 0.617 AC: 2143 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	1.0
Dann	Benign	0.16

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: rs216283; hg19: chr19-3007698;