rs7862187

chr9-79723889-A-Gchr9-79723889-A-T

Variant summary

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

The NM_007005.6(TLE4):c.2214+854A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,218 control chromosomes in the GnomAD database, including 62,487 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 0.91 (62487 hom., cov: 32)
• Consequence: TLE4 NM_007005.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLE4	NM_007005.6	c.2214+854A>G		intron_variant		ENST00000376552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLE4	ENST00000376552.8	c.2214+854A>G		intron_variant		1	NM_007005.6	P1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137808 AN: 152100 Hom.: 62428 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.906 AC: 137929 AN: 152218 Hom.: 62487 Cov.: 32 AF XY: 0.902 AC XY: 67116 AN XY: 74422

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.912

Gnomad4 OTH AF: 0.897

Alfa AF: 0.911 Hom.: 28216

Bravo AF: 0.910

Asia WGS AF: 0.871 AC: 3026 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.15
Dann	Benign	0.44

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: rs7862187; hg19: chr9-82338804;