9-79699494-A-G

Position:

• chr9-79699494-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007005.6(TLE4):​c.610-5289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,132 control chromosomes in the GnomAD database, including 43,328 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 0.75 (43328 hom., cov: 32)
• Consequence: TLE4 NM_007005.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160

Genes affected

TLE4 (HGNC:11840): (TLE family member 4, transcriptional corepressor) Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway. Predicted to act upstream of or within Wnt signaling pathway; cellular response to leukemia inhibitory factor; and negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLE4	NM_007005.6	c.610-5289A>G		intron_variant		ENST00000376552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLE4	ENST00000376552.8	c.610-5289A>G		intron_variant		1	NM_007005.6	P1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114132 AN: 152014 Hom.: 43302 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.751 AC: 114209 AN: 152132 Hom.: 43328 Cov.: 32 AF XY: 0.751 AC XY: 55847 AN XY: 74368

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.762

Alfa AF: 0.782 Hom.: 7596

Bravo AF: 0.745

Asia WGS AF: 0.795 AC: 2764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.39

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: rs1930259; hg19: chr9-82314409;