chr9-79610138-G-A

Variant names:

• chr9-79610138-G-A
• rs2807310
• NM_007005.6:c.253-2518G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_007005.6(TLE4):​c.253-2518G>A variant causes a intron change. The variant allele was found at a frequency of 0.251 in 151,914 control chromosomes in the GnomAD database, including 5,653 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 0.25 (5653 hom., cov: 32)
• Consequence: TLE4 NM_007005.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.55
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE4	NM_007005.6	c.253-2518G>A		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.253-2518G>A		intron_variant	Intron 4 of 19	1	NM_007005.6	ENSP00000365735.2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38053 AN: 151796 Hom.: 5641 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.251 AC: 38098 AN: 151914 Hom.: 5653 Cov.: 32 AF XY: 0.250 AC XY: 18540 AN XY: 74240

African (AFR) AF: 0.418 AC: 17310 AN: 41418

American (AMR) AF: 0.194 AC: 2955 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 911 AN: 3472

East Asian (EAS) AF: 0.166 AC: 856 AN: 5146

South Asian (SAS) AF: 0.180 AC: 866 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2187 AN: 10546

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12348 AN: 67954

Other (OTH) AF: 0.243 AC: 510 AN: 2100

Alfa AF: 0.210 Hom.: 10630

Bravo AF: 0.260

Asia WGS AF: 0.200 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.87
PhyloP100		5.5
Mutation Taster		=99/1	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: rs2807310; hg19: chr9-82225053;