rs1555376234
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_138576.4(BCL11B):c.1495G>T(p.Glu499Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
BCL11B
NM_138576.4 stop_gained
NM_138576.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.24
Genes affected
BCL11B (HGNC:13222): (BCL11 transcription factor B) This gene encodes a C2H2-type zinc finger protein and is closely related to BCL11A, a gene whose translocation may be associated with B-cell malignancies. Although the specific function of this gene has not been determined, the encoded protein is known to be a transcriptional repressor, and is regulated by the NURD nucleosome remodeling and histone deacetylase complex. Four alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 18 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 14-99175341-C-A is Pathogenic according to our data. Variant chr14-99175341-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 560178.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCL11B | NM_138576.4 | c.1495G>T | p.Glu499Ter | stop_gained | 4/4 | ENST00000357195.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCL11B | ENST00000357195.8 | c.1495G>T | p.Glu499Ter | stop_gained | 4/4 | 1 | NM_138576.4 | A2 | |
BCL11B | ENST00000345514.2 | c.1282G>T | p.Glu428Ter | stop_gained | 3/3 | 1 | P4 | ||
BCL11B | ENST00000443726.2 | c.913G>T | p.Glu305Ter | stop_gained | 2/2 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 7.12e-7 AC: 1AN: 1404414Hom.: 0 Cov.: 33 AF XY: 0.00000144 AC XY: 1AN XY: 695366
GnomAD4 exome
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1404414
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33
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1
AN XY:
695366
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 28, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D;D
Vest4
GERP RS
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