Genetic Variant BCL11B:c.*1218A>C (chr14-99172933-T-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_138576.4(BCL11B):c.*1218A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 218,508 control chromosomes in the GnomAD database, including 7,397 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 0.26 ( 5252 hom., cov: 31)

Exomes 𝑓: 0.22 ( 2145 hom. )

Consequence

BCL11B
NM_138576.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.126

Publications

11 publications found

Variant links:

Genes affected

BCL11B (HGNC:13222): (BCL11 transcription factor B) This gene encodes a C2H2-type zinc finger protein and is closely related to BCL11A, a gene whose translocation may be associated with B-cell malignancies. Although the specific function of this gene has not been determined, the encoded protein is known to be a transcriptional repressor, and is regulated by the NURD nucleosome remodeling and histone deacetylase complex. Four alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

BCL11B Gene-Disease associations (from GenCC):

intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P
immunodeficiency 49
Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

BCL11B links:

Genome browser will be placed here

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 (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11B	NM_138576.4 link	c.*1218A>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000357195.8	NP_612808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL11B	ENST00000357195.8 link	c.*1218A>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_138576.4	ENSP00000349723.3
BCL11B	ENST00000345514.2 link	c.*1218A>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000280435.6

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38736

AN:

151586

Hom.:

5251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.234

GnomAD4 exome

AF:

0.224

AC:

14977

AN:

66806

Hom.:

2145

Cov.:

AF XY:

0.227

AC XY:

6981

AN XY:

30812

show subpopulations

African (AFR)

AF:

0.130

AC:

427

AN:

3280

American (AMR)

AF:

0.137

AC:

291

AN:

2120

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

978

AN:

4254

East Asian (EAS)

AF:

0.136

AC:

1390

AN:

10186

South Asian (SAS)

AF:

0.241

AC:

139

AN:

576

European-Finnish (FIN)

AF:

0.313

AC:

AN:

Middle Eastern (MID)

AF:

0.264

AC:

107

AN:

406

European-Non Finnish (NFE)

AF:

0.257

AC:

10372

AN:

40286

Other (OTH)

AF:

0.222

AC:

1253

AN:

5634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

510

1021

1531

2042

2552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.255

AC:

38748

AN:

151702

Hom.:

5252

Cov.:

AF XY:

0.255

AC XY:

18864

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.193

AC:

7987

AN:

41340

American (AMR)

AF:

0.209

AC:

3195

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

954

AN:

3466

East Asian (EAS)

AF:

0.143

AC:

740

AN:

5168

South Asian (SAS)

AF:

0.282

AC:

1353

AN:

4796

European-Finnish (FIN)

AF:

0.298

AC:

3120

AN:

10462

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20460

AN:

67908

Other (OTH)

AF:

0.233

AC:

491

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1430

2861

4291

5722

7152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.267

Hom.:

3648

Bravo

AF:

0.247

Asia WGS

AF:

0.207

AC:

725

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

(source)

DANN

Benign

0.59

PhyloP100

-0.13

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