14-99245057-T-C

Variant names:

• chr14-99245057-T-C
• rs1152793
• NM_138576.4:c.427+12414A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BCL11B	NM_138576.4	c.427+12414A>G		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.427+12414A>G		intron_variant	Intron 2 of 3	1	NM_138576.4	ENSP00000349723.3
BCL11B	ENST00000345514.2	c.427+12414A>G		intron_variant	Intron 2 of 2	1		ENSP00000280435.6
BCL11B	ENST00000443726.2	c.58+26104A>G		intron_variant	Intron 1 of 1	5		ENSP00000387419.2

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

African (AFR) AF: 0.161 AC: 6691 AN: 41516

American (AMR) AF: 0.286 AC: 4380 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1961 AN: 5168

South Asian (SAS) AF: 0.461 AC: 2222 AN: 4818

European-Finnish (FIN) AF: 0.246 AC: 2605 AN: 10590

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18994 AN: 67980

Other (OTH) AF: 0.283 AC: 598 AN: 2112

Alfa AF: 0.275 Hom.: 19614

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1152793; hg19: chr14-99711394;