NM_007005.6:c.2214+854A>G

Variant names:

• chr9-79723889-A-G
• rs7862187
• NM_007005.6:c.2214+854A>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.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
• 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=-0.93).
• 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 rank	MANE	Protein	UniProt
TLE4	NM_007005.6	c.2214+854A>G		intron_variant	Intron 19 of 19	ENST00000376552.8	NP_008936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE4	ENST00000376552.8	c.2214+854A>G		intron_variant	Intron 19 of 19	1	NM_007005.6	ENSP00000365735.2

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

African (AFR) AF: 0.913 AC: 37905 AN: 41536

American (AMR) AF: 0.909 AC: 13906 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3144 AN: 3468

East Asian (EAS) AF: 0.856 AC: 4424 AN: 5168

South Asian (SAS) AF: 0.885 AC: 4276 AN: 4830

European-Finnish (FIN) AF: 0.866 AC: 9169 AN: 10590

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.912 AC: 62057 AN: 68016

Other (OTH) AF: 0.897 AC: 1892 AN: 2110

Alfa AF: 0.911 Hom.: 31436

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
PhyloP100		-0.84
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: rs7862187; hg19: chr9-82338804;