Genetic Variant NM_022893.4:c.386-12629G>A (chr2-60481462-C-T) – 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.386-12629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,744 control chromosomes in the GnomAD database, including 31,062 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 0.62 ( 31062 hom., cov: 30)

Consequence

BCL11A
NM_022893.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 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.386-12629G>A	intron	N/A	NP_075044.2
BCL11A	NM_001405708.1		c.386-12629G>A	intron	N/A	NP_001392637.1
BCL11A	NM_001405709.1		c.386-12629G>A	intron	N/A	NP_001392638.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BCL11A	ENST00000642384.2	MANE Select	c.386-12629G>A	intron	N/A	ENSP00000496168.1
BCL11A	ENST00000335712.11	TSL:1	c.386-19038G>A	intron	N/A	ENSP00000338774.7
BCL11A	ENST00000358510.6	TSL:1	c.386-19038G>A	intron	N/A	ENSP00000351307.5

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94626

AN:

151626

Hom.:

31043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.611

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.0305

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.614

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

GnomAD4 genome

AF:

0.624

AC:

94676

AN:

151744

Hom.:

31062

Cov.:

AF XY:

0.609

AC XY:

45156

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.683

AC:

28193

AN:

41274

American (AMR)

AF:

0.486

AC:

7415

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2013

AN:

3466

East Asian (EAS)

AF:

0.0303

AC:

157

AN:

5176

South Asian (SAS)

AF:

0.412

AC:

1978

AN:

4802

European-Finnish (FIN)

AF:

0.615

AC:

6468

AN:

10520

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.684

AC:

46442

AN:

67938

Other (OTH)

AF:

0.608

AC:

1280

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1632

3264

4896

6528

8160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.648

Hom.:

70231

Bravo

AF:

0.614

Asia WGS

AF:

0.275

AC:

961

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.9

(source)

DANN

Benign

0.68

PhyloP100

1.4

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