rs216283

Variant names:

• chr19-3007700-A-C
• rs216283
• NM_003260.5:c.1251-1031T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

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 = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003260.5. 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
	TLE2	NM_003260.5	MANE Select	c.1251-1031T>G		intron	N/A	NP_003251.2
	TLE2	NM_001300846.2		c.1254-1031T>G		intron	N/A	NP_001287775.1
	TLE2	NM_001144761.2		c.1293-1031T>G		intron	N/A	NP_001138233.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE2	ENST00000262953.11	TSL:1 MANE Select	c.1251-1031T>G		intron	N/A	ENSP00000262953.5
	TLE2	ENST00000590536.5	TSL:1	c.1254-1031T>G		intron	N/A	ENSP00000466542.1
	TLE2	ENST00000591529.5	TSL:1	c.1293-1031T>G		intron	N/A	ENSP00000468279.1

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

African (AFR) AF: 0.814 AC: 33810 AN: 41516

American (AMR) AF: 0.613 AC: 9358 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1988 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3628 AN: 5178

South Asian (SAS) AF: 0.468 AC: 2260 AN: 4824

European-Finnish (FIN) AF: 0.539 AC: 5691 AN: 10562

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.584 AC: 39674 AN: 67946

Other (OTH) AF: 0.635 AC: 1341 AN: 2112

Alfa AF: 0.600 Hom.: 17389

Bravo AF: 0.664

Asia WGS AF: 0.617 AC: 2143 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	1.0
DANN	Benign	0.16
PhyloP100		-2.4
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: rs216283; hg19: chr19-3007698;