dbSNP rs2556377: BCL11A:c.385+12469C>T (chr2-60533502-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_022893.4(BCL11A):c.385+12469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,200 control chromosomes in the GnomAD database, including 48,708 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 0.80 ( 48704 hom., cov: 32)

Exomes 𝑓: 0.69 ( 4 hom. )

Consequence

BCL11A
NM_022893.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.257

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11A	NM_022893.4 link	c.385+12469C>T		intron_variant	Intron 2 of 3	ENST00000642384.2	NP_075044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL11A	ENST00000642384.2 link	c.385+12469C>T		intron_variant	Intron 2 of 3		NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121395

AN:

152066

Hom.:

48656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.778

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.836

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.837

Gnomad OTH

AF:

0.799

GnomAD4 exome

AF:

0.688

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.700

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.798

AC:

121502

AN:

152184

Hom.:

48704

Cov.:

AF XY:

0.795

AC XY:

59129

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.750

AC:

31139

AN:

41504

American (AMR)

AF:

0.778

AC:

11898

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.749

AC:

2602

AN:

3472

East Asian (EAS)

AF:

0.766

AC:

3976

AN:

5188

South Asian (SAS)

AF:

0.836

AC:

4031

AN:

4822

European-Finnish (FIN)

AF:

0.776

AC:

8208

AN:

10578

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.837

AC:

56923

AN:

68000

Other (OTH)

AF:

0.800

AC:

1692

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1275

2550

3824

5099

6374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.815

Hom.:

56306

Bravo

AF:

0.795

Asia WGS

AF:

0.805

AC:

2796

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.5

(source)

DANN

Benign

0.93

PhyloP100

-0.26

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over