rs1291490

chr4-108072856-C-T

Variant summary

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

The NM_016269.5(LEF1):c.1009-2086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,224 control chromosomes in the GnomAD database, including 1,402 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 (1401 hom., cov: 33)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: LEF1 NM_016269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

Genes affected

LEF1 (HGNC:6551): (lymphoid enhancer binding factor 1) This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. The protein encoded by this gene can bind to a functionally important site in the T-cell receptor-alpha enhancer, thereby conferring maximal enhancer activity. This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. Mutations in this gene have been found in somatic sebaceous tumors. This gene has also been linked to other cancers, including androgen-independent prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LEF1	NM_016269.5	c.1009-2086G>A		intron_variant		ENST00000265165.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEF1	ENST00000265165.6	c.1009-2086G>A		intron_variant		1	NM_016269.5

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18089 AN: 152082 Hom.: 1401 Cov.: 33

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.167 AC: 4 AN: 24 Hom.: 1 Cov.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.119 AC: 18082 AN: 152200 Hom.: 1401 Cov.: 33 AF XY: 0.120 AC XY: 8923 AN XY: 74400

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0506

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.127

Alfa AF: 0.153 Hom.: 2561

Bravo AF: 0.108

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.8
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1291490; hg19: chr4-108994012;