rs2228173

Positions:

• chr9-81652232-T-C
• chr9-81652232-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005077.5(TLE1):​c.354A>G​(p.Glu118Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,613,660 control chromosomes in the GnomAD database, including 664,639 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 0.91 (62677 hom., cov: 31)
  • Exomes 𝑓: 0.91 (601962 hom.)
• Consequence: TLE1 NM_005077.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=3.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLE1	NM_005077.5	c.354A>G	p.Glu118Glu	synonymous_variant	6/20	ENST00000376499.8	NP_005068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLE1	ENST00000376499.8	c.354A>G	p.Glu118Glu	synonymous_variant	6/20	1	NM_005077.5	ENSP00000365682.3
TLE1	ENST00000418319.5	c.354A>G	p.Glu118Glu	synonymous_variant	6/9	5		ENSP00000391347.1
TLE1	ENST00000376463.3	c.264A>G	p.Glu88Glu	synonymous_variant	5/6	2		ENSP00000365646.2

Frequencies

GnomAD3 genomes AF: 0.908 AC: 137936 AN: 151936 Hom.: 62615 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.895

GnomAD3 exomes AF: 0.910 AC: 228864 AN: 251396 Hom.: 104237 AF XY: 0.909 AC XY: 123544 AN XY: 135866

Gnomad AFR exome AF: 0.907

Gnomad AMR exome AF: 0.950

Gnomad ASJ exome AF: 0.894

Gnomad EAS exome AF: 0.880

Gnomad SAS exome AF: 0.915

Gnomad FIN exome AF: 0.913

Gnomad NFE exome AF: 0.904

Gnomad OTH exome AF: 0.906

GnomAD4 exome AF: 0.907 AC: 1326145 AN: 1461606 Hom.: 601962 Cov.: 53 AF XY: 0.907 AC XY: 659468 AN XY: 727092

Gnomad4 AFR exome AF: 0.913

Gnomad4 AMR exome AF: 0.948

Gnomad4 ASJ exome AF: 0.889

Gnomad4 EAS exome AF: 0.892

Gnomad4 SAS exome AF: 0.916

Gnomad4 FIN exome AF: 0.911

Gnomad4 NFE exome AF: 0.906

Gnomad4 OTH exome AF: 0.903

GnomAD4 genome AF: 0.908 AC: 138057 AN: 152054 Hom.: 62677 Cov.: 31 AF XY: 0.908 AC XY: 67494 AN XY: 74322

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.922

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.896

Alfa AF: 0.908 Hom.: 43526

Bravo AF: 0.906

Asia WGS AF: 0.907 AC: 3155 AN: 3478

EpiCase AF: 0.903

EpiControl AF: 0.898

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.5
DANN	Benign	0.58

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: rs2228173; hg19: chr9-84267147;