rs2228173

Variant names:

• chr9-81652232-T-C
• rs2228173
• NM_005077.5:c.354A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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]

TLE1 Gene-Disease associations (from GenCC):

• movement disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TLE1	NM_005077.5	c.354A>G	p.Glu118Glu	synonymous_variant	Exon 6 of 20	ENST00000376499.8	NP_005068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE1	ENST00000376499.8	c.354A>G	p.Glu118Glu	synonymous_variant	Exon 6 of 20	1	NM_005077.5	ENSP00000365682.3
TLE1	ENST00000418319.5	c.354A>G	p.Glu118Glu	synonymous_variant	Exon 6 of 9	5		ENSP00000391347.1
TLE1	ENST00000376463.3	c.264A>G	p.Glu88Glu	synonymous_variant	Exon 5 of 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

GnomAD2 exomes AF: 0.910 AC: 228864 AN: 251396 AF XY: 0.909

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 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

African (AFR) AF: 0.913 AC: 30571 AN: 33476

American (AMR) AF: 0.948 AC: 42404 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 23222 AN: 26132

East Asian (EAS) AF: 0.892 AC: 35427 AN: 39698

South Asian (SAS) AF: 0.916 AC: 78955 AN: 86218

European-Finnish (FIN) AF: 0.911 AC: 48629 AN: 53404

Middle Eastern (MID) AF: 0.875 AC: 5044 AN: 5764

European-Non Finnish (NFE) AF: 0.906 AC: 1007359 AN: 1111810

Other (OTH) AF: 0.903 AC: 54534 AN: 60388

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

African (AFR) AF: 0.911 AC: 37770 AN: 41478

American (AMR) AF: 0.915 AC: 13956 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3088 AN: 3470

East Asian (EAS) AF: 0.880 AC: 4523 AN: 5138

South Asian (SAS) AF: 0.922 AC: 4448 AN: 4826

European-Finnish (FIN) AF: 0.922 AC: 9740 AN: 10568

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61629 AN: 68006

Other (OTH) AF: 0.896 AC: 1887 AN: 2106

Alfa AF: 0.908 Hom.: 48551

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
PhyloP100		3.3
Mutation Taster		=254/46	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: rs2228173; hg19: chr9-84267147; COSMIC: COSV108223557;