rs1688128

Variant names:

• chr19-3030170-T-C
• rs1688128
• ENST00000591529.5:c.64-1367A>G

Variant summary

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

The ENST00000591529.5(TLE2):​c.64-1367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,958 control chromosomes in the GnomAD database, including 20,595 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 0.51 (20595 hom., cov: 31)
• Consequence: TLE2 ENST00000591529.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE2	NM_001144761.2	c.64-1367A>G		intron_variant	Intron 2 of 19		NP_001138233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE2	ENST00000591529.5	c.64-1367A>G		intron_variant	Intron 2 of 19	1		ENSP00000468279.1
TLE2	ENST00000426948.6	c.64-1367A>G		intron_variant	Intron 1 of 18	5		ENSP00000392869.2
TLE2	ENST00000591457.5	c.4-1367A>G		intron_variant	Intron 1 of 6	5		ENSP00000467337.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77812 AN: 151840 Hom.: 20557 Cov.: 31

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.513 AC: 77910 AN: 151958 Hom.: 20595 Cov.: 31 AF XY: 0.511 AC XY: 37961 AN XY: 74256

African (AFR) AF: 0.645 AC: 26733 AN: 41434

American (AMR) AF: 0.509 AC: 7764 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1844 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1853 AN: 5168

South Asian (SAS) AF: 0.383 AC: 1836 AN: 4800

European-Finnish (FIN) AF: 0.514 AC: 5430 AN: 10560

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30806 AN: 67954

Other (OTH) AF: 0.515 AC: 1088 AN: 2112

Alfa AF: 0.481 Hom.: 51175

Bravo AF: 0.523

Asia WGS AF: 0.364 AC: 1267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.53
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1688128; hg19: chr19-3030168;