4-108079590-ACC-CGA

Variant names:

• chr4-108079590-ACC-CGA
• NM_016269.5:c.745_747delGGTinsTCG
• LEF1 p.Gly249Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016269.5(LEF1):​c.745_747delGGTinsTCG​(p.Gly249Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G249D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LEF1 NM_016269.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.11
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016269.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEF1	NM_016269.5	MANE Select	c.745_747delGGTinsTCG	p.Gly249Ser	missense	N/A	NP_057353.1	Q9UJU2-1
	LEF1	NM_001130714.3		c.661_663delGGTinsTCG	p.Gly221Ser	missense	N/A	NP_001124186.1	Q9UJU2-6
	LEF1	NM_001130713.3		c.661_663delGGTinsTCG	p.Gly221Ser	missense	N/A	NP_001124185.1	Q9UJU2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEF1	ENST00000265165.6	TSL:1 MANE Select	c.745_747delGGTinsTCG	p.Gly249Ser	missense	N/A	ENSP00000265165.1	Q9UJU2-1
	LEF1	ENST00000379951.6	TSL:1	c.661_663delGGTinsTCG	p.Gly221Ser	missense	N/A	ENSP00000369284.2	Q9UJU2-6
	LEF1	ENST00000438313.6	TSL:1	c.661_663delGGTinsTCG	p.Gly221Ser	missense	N/A	ENSP00000406176.2	Q9UJU2-5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-109000746;