Genetic Variant BCL11A:c.386-26273T>C (chr2-60495106-A-G) – 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.386-26273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,102 control chromosomes in the GnomAD database, including 5,212 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 0.25 ( 5212 hom., cov: 32)

Consequence

BCL11A
NM_022893.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0240

Publications

17 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:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 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.386-26273T>C	intron	N/A	NP_075044.2
BCL11A	NM_001405708.1		c.386-26273T>C	intron	N/A	NP_001392637.1
BCL11A	NM_001405709.1		c.386-26273T>C	intron	N/A	NP_001392638.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BCL11A	ENST00000642384.2	MANE Select	c.386-26273T>C	intron	N/A	ENSP00000496168.1
BCL11A	ENST00000335712.11	TSL:1	c.386-32682T>C	intron	N/A	ENSP00000338774.7
BCL11A	ENST00000358510.6	TSL:1	c.386-32682T>C	intron	N/A	ENSP00000351307.5

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38652

AN:

151984

Hom.:

5203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.00848

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.241

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

GnomAD4 genome

AF:

0.254

AC:

38688

AN:

152102

Hom.:

5212

Cov.:

AF XY:

0.246

AC XY:

18256

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.282

AC:

11701

AN:

41478

American (AMR)

AF:

0.196

AC:

3000

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

722

AN:

3468

East Asian (EAS)

AF:

0.00850

AC:

AN:

5178

South Asian (SAS)

AF:

0.118

AC:

569

AN:

4830

European-Finnish (FIN)

AF:

0.262

AC:

2773

AN:

10584

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19066

AN:

67954

Other (OTH)

AF:

0.238

AC:

503

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1477

2954

4431

5908

7385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.263

Hom.:

12390

Bravo

AF:

0.250

Asia WGS

AF:

0.0800

AC:

281

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.4

(source)

DANN

Benign

0.53

PhyloP100

-0.024

Mutation Taster

=100/0

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