14-99174164-GC-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_138576.4(BCL11B):c.2671del(p.Ala891ProfsTer106) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCL11B NM_138576.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 910 codons.
• PP5: Variant 14-99174164-GC-G is Pathogenic according to our data. Variant chr14-99174164-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 560176.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.2671del	p.Ala891ProfsTer106	frameshift_variant	4/4	ENST00000357195.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL11B	ENST00000357195.8	c.2671del	p.Ala891ProfsTer106	frameshift_variant	4/4	1	NM_138576.4	A2
BCL11B	ENST00000345514.2	c.2458del	p.Ala820ProfsTer106	frameshift_variant	3/3	1		P4
BCL11B	ENST00000443726.2	c.2089del	p.Ala697ProfsTer?	frameshift_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

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: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1555376017; hg19: chr14-99640501;