9-79600997-C-T

Variant names:

• chr9-79600997-C-T
• rs2807312
• NM_007005.6:c.253-11659C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007005.6(TLE4):​c.253-11659C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,188 control chromosomes in the GnomAD database, including 753 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 0.089 (753 hom., cov: 32)
• Consequence: TLE4 NM_007005.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE4	NM_007005.6	c.253-11659C>T		intron_variant	Intron 4 of 19	ENST00000376552.8	NP_008936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE4	ENST00000376552.8	c.253-11659C>T		intron_variant	Intron 4 of 19	1	NM_007005.6	ENSP00000365735.2

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13618 AN: 152070 Hom.: 754 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0991

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

GnomAD4 genome AF: 0.0894 AC: 13609 AN: 152188 Hom.: 753 Cov.: 32 AF XY: 0.0949 AC XY: 7059 AN XY: 74392

African (AFR) AF: 0.0208 AC: 866 AN: 41538

American (AMR) AF: 0.0931 AC: 1424 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3472

East Asian (EAS) AF: 0.138 AC: 714 AN: 5170

South Asian (SAS) AF: 0.126 AC: 607 AN: 4820

European-Finnish (FIN) AF: 0.176 AC: 1859 AN: 10574

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7381 AN: 68000

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.102 Hom.: 687

Bravo AF: 0.0803

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.43
PhyloP100		0.018
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: rs2807312; hg19: chr9-82215912;