14-99172933-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BCL11B	NM_138576.4	c.*1218A>C		3_prime_UTR_variant	4/4	ENST00000357195.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL11B	ENST00000357195.8	c.*1218A>C		3_prime_UTR_variant	4/4	1	NM_138576.4	A2
BCL11B	ENST00000345514.2	c.*1218A>C		3_prime_UTR_variant	3/3	1		P4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38736 AN: 151586 Hom.: 5251 Cov.: 31

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.: 0 AF XY: 0.227 AC XY: 6981 AN XY: 30812

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.255 AC: 38748 AN: 151702 Hom.: 5252 Cov.: 31 AF XY: 0.255 AC XY: 18864 AN XY: 74102

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.233

Alfa AF: 0.266 Hom.: 2385

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
Dann	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs1152781; hg19: chr14-99639270;