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GeneBe

4-108163655-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_016269.5(LEF1):c.327G>A(p.Ser109=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,780 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00078 ( 11 hom. )

Consequence

LEF1
NM_016269.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.78
Variant links:
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 Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-108163655-C-T is Benign according to our data. Variant chr4-108163655-C-T is described in ClinVar as [Benign]. Clinvar id is 783383.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.78 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00499 (759/152208) while in subpopulation AFR AF= 0.0167 (693/41538). AF 95% confidence interval is 0.0157. There are 3 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 757 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LEF1NM_016269.5 linkuse as main transcriptc.327G>A p.Ser109= synonymous_variant 3/12 ENST00000265165.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LEF1ENST00000265165.6 linkuse as main transcriptc.327G>A p.Ser109= synonymous_variant 3/121 NM_016269.5 Q9UJU2-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00498
AC:
757
AN:
152090
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0167
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00174
AC:
437
AN:
251338
Hom.:
4
AF XY:
0.00129
AC XY:
175
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.0171
Gnomad AMR exome
AF:
0.00202
Gnomad ASJ exome
AF:
0.00526
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.000785
AC:
1147
AN:
1461572
Hom.:
11
Cov.:
30
AF XY:
0.000679
AC XY:
494
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.0185
Gnomad4 AMR exome
AF:
0.00230
Gnomad4 ASJ exome
AF:
0.00452
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000187
Gnomad4 OTH exome
AF:
0.00141
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00499
AC:
759
AN:
152208
Hom.:
3
Cov.:
32
AF XY:
0.00461
AC XY:
343
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0167
Gnomad4 AMR
AF:
0.00190
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00210
Hom.:
0
Bravo
AF:
0.00584
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000654
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
4.8
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61751709; hg19: chr4-109084811; COSMIC: COSV54471465; COSMIC: COSV54471465; API