chr9-79703554-A-G

Variant names:

• chr9-79703554-A-G
• rs1547275
• NM_007005.6:c.610-1229A>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.610-1229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,180 control chromosomes in the GnomAD database, including 1,187 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 0.12 (1187 hom., cov: 32)
• Consequence: TLE4 NM_007005.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE4	NM_007005.6	c.610-1229A>G		intron_variant	Intron 8 of 19	ENST00000376552.8	NP_008936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE4	ENST00000376552.8	c.610-1229A>G		intron_variant	Intron 8 of 19	1	NM_007005.6	ENSP00000365735.2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17646 AN: 152062 Hom.: 1188 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.116 AC: 17661 AN: 152180 Hom.: 1187 Cov.: 32 AF XY: 0.111 AC XY: 8296 AN XY: 74434

African (AFR) AF: 0.180 AC: 7447 AN: 41486

American (AMR) AF: 0.0813 AC: 1244 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3470

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5184

South Asian (SAS) AF: 0.0483 AC: 233 AN: 4822

European-Finnish (FIN) AF: 0.0714 AC: 757 AN: 10606

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6937 AN: 68002

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.0753 Hom.: 138

Bravo AF: 0.122

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.67
PhyloP100		1.8
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: rs1547275; hg19: chr9-82318469;