chr4-108064359-T-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_016269.5(LEF1):āc.1142A>Gā(p.Glu381Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,611,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 31)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
LEF1
NM_016269.5 missense
NM_016269.5 missense
Scores
7
10
2
Clinical Significance
Conservation
PhyloP100: 6.63
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEF1 | NM_016269.5 | c.1142A>G | p.Glu381Gly | missense_variant | 10/12 | ENST00000265165.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEF1 | ENST00000265165.6 | c.1142A>G | p.Glu381Gly | missense_variant | 10/12 | 1 | NM_016269.5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152174Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251140Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135728
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459680Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726328
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152174Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74330
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | The c.1142A>G (p.E381G) alteration is located in exon 10 (coding exon 10) of the LEF1 gene. This alteration results from a A to G substitution at nucleotide position 1142, causing the glutamic acid (E) at amino acid position 381 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;B;B;.
Vest4
MutPred
Gain of glycosylation at S386 (P = 0.0283);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at