9-79699494-A-G

Variant names:

• chr9-79699494-A-G
• rs1930259
• NM_007005.6:c.610-5289A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007005.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE4	NM_007005.6	MANE Select	c.610-5289A>G		intron	N/A	NP_008936.2
	TLE4	NM_001282748.2		c.610-5289A>G		intron	N/A	NP_001269677.1
	TLE4	NM_001351541.2		c.649-5289A>G		intron	N/A	NP_001338470.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE4	ENST00000376552.8	TSL:1 MANE Select	c.610-5289A>G		intron	N/A	ENSP00000365735.2
	TLE4	ENST00000376537.8	TSL:1	c.610-5289A>G		intron	N/A	ENSP00000365720.4
	TLE4	ENST00000376544.7	TSL:1	c.610-5289A>G		intron	N/A	ENSP00000365727.4

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

African (AFR) AF: 0.626 AC: 25994 AN: 41492

American (AMR) AF: 0.805 AC: 12303 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2544 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4029 AN: 5174

South Asian (SAS) AF: 0.830 AC: 3997 AN: 4818

European-Finnish (FIN) AF: 0.788 AC: 8334 AN: 10580

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54376 AN: 68002

Other (OTH) AF: 0.762 AC: 1610 AN: 2114

Alfa AF: 0.777 Hom.: 7746

Bravo AF: 0.745

Asia WGS AF: 0.795 AC: 2764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.39
PhyloP100		0.16
Mutation Taster		=100/0	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: rs1930259; hg19: chr9-82314409;