rs216276

Variant names:

• chr19-3004794-G-A
• rs216276
• NM_003260.5:c.1896+643C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003260.5(TLE2):​c.1896+643C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,812 control chromosomes in the GnomAD database, including 5,856 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 (5856 hom., cov: 30)
• Consequence: TLE2 NM_003260.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE2	NM_003260.5	c.1896+643C>T		intron_variant	Intron 17 of 19	ENST00000262953.11	NP_003251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE2	ENST00000262953.11	c.1896+643C>T		intron_variant	Intron 17 of 19	1	NM_003260.5	ENSP00000262953.5

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28631 AN: 151694 Hom.: 5847 Cov.: 30

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0498

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.189 AC: 28683 AN: 151812 Hom.: 5856 Cov.: 30 AF XY: 0.184 AC XY: 13658 AN XY: 74192

African (AFR) AF: 0.513 AC: 21176 AN: 41304

American (AMR) AF: 0.102 AC: 1554 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.0494 AC: 238 AN: 4814

European-Finnish (FIN) AF: 0.0939 AC: 994 AN: 10582

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0627 AC: 4258 AN: 67964

Other (OTH) AF: 0.141 AC: 298 AN: 2106

Alfa AF: 0.110 Hom.: 2850

Bravo AF: 0.203

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.99
DANN	Benign	0.35
PhyloP100		-0.52
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: rs216276; hg19: chr19-3004792;