rs1152793

chr14-99245057-T-C

Variant summary

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

The NM_138576.4(BCL11B):c.427+12414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,148 control chromosomes in the GnomAD database, including 5,442 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 (5442 hom., cov: 33)
• Consequence: BCL11B NM_138576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL11B	NM_138576.4	c.427+12414A>G		intron_variant		ENST00000357195.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL11B	ENST00000357195.8	c.427+12414A>G		intron_variant		1	NM_138576.4	A2
BCL11B	ENST00000345514.2	c.427+12414A>G		intron_variant		1		P4
BCL11B	ENST00000443726.2	c.58+26104A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38942 AN: 152030 Hom.: 5443 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.256 AC: 38963 AN: 152148 Hom.: 5442 Cov.: 33 AF XY: 0.259 AC XY: 19254 AN XY: 74384

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.283

Alfa AF: 0.282 Hom.: 8346

Bravo AF: 0.252

Asia WGS AF: 0.426 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	7.6
Dann	Benign	0.46

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: rs1152793; hg19: chr14-99711394;