14-99244506-C-T

Variant names:

• chr14-99244506-C-T
• rs1152790
• NM_138576.4:c.428-12949G>A

Variant summary

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

The NM_138576.4(BCL11B):​c.428-12949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,018 control chromosomes in the GnomAD database, including 25,467 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 0.57 (25467 hom., cov: 32)
• Consequence: BCL11B NM_138576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11B	NM_138576.4	c.428-12949G>A		intron_variant	Intron 2 of 3	ENST00000357195.8	NP_612808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL11B	ENST00000357195.8	c.428-12949G>A		intron_variant	Intron 2 of 3	1	NM_138576.4	ENSP00000349723.3
BCL11B	ENST00000345514.2	c.427+12965G>A		intron_variant	Intron 2 of 2	1		ENSP00000280435.6
BCL11B	ENST00000443726.2	c.58+26655G>A		intron_variant	Intron 1 of 1	5		ENSP00000387419.2

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86790 AN: 151900 Hom.: 25456 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.571 AC: 86840 AN: 152018 Hom.: 25467 Cov.: 32 AF XY: 0.576 AC XY: 42766 AN XY: 74288

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.580

Alfa AF: 0.513 Hom.: 32886

Bravo AF: 0.586

Asia WGS AF: 0.765 AC: 2662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.87

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: rs1152790; hg19: chr14-99710843;