9-81593124-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_005077.5(TLE1):c.1482C>T(p.Asn494=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00482 in 1,614,148 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (25 hom.)
• Consequence: TLE1 NM_005077.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.92

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 9-81593124-G-A is Benign according to our data. Variant chr9-81593124-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659272.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 566 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLE1	NM_005077.5	c.1482C>T	p.Asn494=	synonymous_variant	15/20	ENST00000376499.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLE1	ENST00000376499.8	c.1482C>T	p.Asn494=	synonymous_variant	15/20	1	NM_005077.5	P1

Frequencies

GnomAD3 genomes AF: 0.00372 AC: 566 AN: 152138 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00538

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00404 AC: 1016 AN: 251470 Hom.: 3 AF XY: 0.00403 AC XY: 548 AN XY: 135908

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00744

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00163

Gnomad FIN exome AF: 0.00333

Gnomad NFE exome AF: 0.00570

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.00494 AC: 7216 AN: 1461892 Hom.: 25 Cov.: 32 AF XY: 0.00488 AC XY: 3550 AN XY: 727246

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00378

Gnomad4 ASJ exome AF: 0.00895

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00152

Gnomad4 FIN exome AF: 0.00339

Gnomad4 NFE exome AF: 0.00550

Gnomad4 OTH exome AF: 0.00546

GnomAD4 genome AF: 0.00372 AC: 566 AN: 152256 Hom.: 1 Cov.: 32 AF XY: 0.00360 AC XY: 268 AN XY: 74452

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00538

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00506 Hom.: 0

Bravo AF: 0.00377

EpiCase AF: 0.00660

EpiControl AF: 0.00717

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

TLE1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	8.4
Dann	Benign	0.78

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: rs61733324; hg19: chr9-84208039;