Genetic Variant BCL11A:c.386-29483C>G (chr2-60498316-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022893.4(BCL11A):c.386-29483C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,546 control chromosomes in the GnomAD database, including 12,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 12021 hom., cov: 30)

Consequence

BCL11A
NM_022893.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

52 publications found

Variant links:

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]

BCL11A Gene-Disease associations (from GenCC):

Dias-Logan syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Ambry Genetics, G2P, Illumina

BCL11A links:

ENSG00000233953 (HGNC:):

ENSG00000233953 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022893.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BCL11A	NM_022893.4	MANE Select	c.386-29483C>G	intron	N/A	NP_075044.2
BCL11A	NM_001405708.1		c.386-29483C>G	intron	N/A	NP_001392637.1
BCL11A	NM_001405709.1		c.386-29483C>G	intron	N/A	NP_001392638.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BCL11A	ENST00000642384.2	MANE Select	c.386-29483C>G	intron	N/A	ENSP00000496168.1
BCL11A	ENST00000335712.11	TSL:1	c.386-35892C>G	intron	N/A	ENSP00000338774.7
BCL11A	ENST00000358510.6	TSL:1	c.386-35892C>G	intron	N/A	ENSP00000351307.5

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58521

AN:

151430

Hom.:

12001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.0120

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.387

AC:

58584

AN:

151546

Hom.:

12021

Cov.:

AF XY:

0.375

AC XY:

27762

AN XY:

74010

show subpopulations

African (AFR)

AF:

0.437

AC:

18051

AN:

41292

American (AMR)

AF:

0.303

AC:

4614

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1157

AN:

3466

East Asian (EAS)

AF:

0.0123

AC:

AN:

5138

South Asian (SAS)

AF:

0.190

AC:

902

AN:

4752

European-Finnish (FIN)

AF:

0.380

AC:

3987

AN:

10502

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.422

AC:

28602

AN:

67854

Other (OTH)

AF:

0.375

AC:

789

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1727

3455

5182

6910

8637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.270

Hom.:

644

Bravo

AF:

0.381

Asia WGS

AF:

0.122

AC:

425

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.7

(source)

DANN

Benign

0.61

PhyloP100

1.4

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over