2-60452646-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000356842.9(BCL11A):c.2251C>T(p.Arg751Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
BCL11A
ENST00000356842.9 missense
ENST00000356842.9 missense
Scores
2
2
11
Clinical Significance
Conservation
PhyloP100: 4.34
Genes affected
BCL11A (HGNC:13221): (BCL11 transcription factor A) This gene encodes a C2H2 type zinc-finger protein by its similarity to the mouse Bcl11a/Evi9 protein. The corresponding mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.075792074).
BS2
High AC in GnomAdExome4 at 38 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCL11A | NM_018014.4 | c.2251C>T | p.Arg751Trp | missense_variant | 5/5 | ||
BCL11A | NM_001405719.1 | c.2149C>T | p.Arg717Trp | missense_variant | 4/4 | ||
BCL11A | NM_001405722.1 | c.2095C>T | p.Arg699Trp | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCL11A | ENST00000356842.9 | c.2251C>T | p.Arg751Trp | missense_variant | 5/5 | 1 | |||
BCL11A | ENST00000358510.6 | c.2301C>T | p.Phe767= | synonymous_variant | 4/4 | 1 | |||
BCL11A | ENST00000359629.10 | c.651C>T | p.Phe217= | synonymous_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152080Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250954Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135658
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GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461650Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 727140
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152080Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74300
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | BCL11A: PP2, BP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MVP
ClinPred
T
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at