chr14-99175639-G-GGGGCT
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_138576.4(BCL11B):c.1196_1197insAGCCC(p.Lys400AlafsTer7) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
BCL11B
NM_138576.4 frameshift
NM_138576.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.41
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 Pathogenic. Variant got 12 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 24 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-99175639-G-GGGGCT is Pathogenic according to our data. Variant chr14-99175639-G-GGGGCT is described in ClinVar as [Pathogenic]. Clinvar id is 521135.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCL11B | NM_138576.4 | c.1196_1197insAGCCC | p.Lys400AlafsTer7 | frameshift_variant | 4/4 | ENST00000357195.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCL11B | ENST00000357195.8 | c.1196_1197insAGCCC | p.Lys400AlafsTer7 | frameshift_variant | 4/4 | 1 | NM_138576.4 | A2 | |
BCL11B | ENST00000345514.2 | c.983_984insAGCCC | p.Lys329AlafsTer7 | frameshift_variant | 3/3 | 1 | P4 | ||
BCL11B | ENST00000443726.2 | c.614_615insAGCCC | p.Lys206AlafsTer7 | frameshift_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 18, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at