chr4-108125804-G-A

Position:

• chr4-108125804-G-A

Variant summary

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

The NM_016269.5(LEF1):​c.415-36547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,672 control chromosomes in the GnomAD database, including 17,488 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 0.45 (17488 hom., cov: 30)
• Consequence: LEF1 NM_016269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LEF1	NM_016269.5	c.415-36547C>T		intron_variant		ENST00000265165.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEF1	ENST00000265165.6	c.415-36547C>T		intron_variant		1	NM_016269.5

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68881 AN: 151556 Hom.: 17485 Cov.: 30

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.454 AC: 68907 AN: 151672 Hom.: 17488 Cov.: 30 AF XY: 0.450 AC XY: 33379 AN XY: 74118

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.516

Alfa AF: 0.563 Hom.: 32734

Bravo AF: 0.440

Asia WGS AF: 0.422 AC: 1467 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.55
DANN	Benign	0.76

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: rs956237; hg19: chr4-109046960;