rs3994992

Positions:

• chr14-99213170-C-T

Variant summary

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

The NM_138576.4(BCL11B):​c.640+18175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,042 control chromosomes in the GnomAD database, including 9,204 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 0.32 (9204 hom., cov: 31)
• Consequence: BCL11B NM_138576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946

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]

LOC124903412 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL11B	NM_138576.4	c.640+18175G>A		intron_variant		ENST00000357195.8	NP_612808.1
LOC124903412	XR_007064392.1	n.1167G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL11B	ENST00000357195.8	c.640+18175G>A		intron_variant		1	NM_138576.4	ENSP00000349723	A2
BCL11B	ENST00000345514.2	c.428-36975G>A		intron_variant		1		ENSP00000280435	P4
BCL11B	ENST00000443726.2	c.59-36975G>A		intron_variant		5		ENSP00000387419

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48325 AN: 151922 Hom.: 9211 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.318 AC: 48326 AN: 152042 Hom.: 9204 Cov.: 31 AF XY: 0.312 AC XY: 23206 AN XY: 74330

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.0415

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.339

Alfa AF: 0.415 Hom.: 22888

Bravo AF: 0.306

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.9
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: rs3994992; hg19: chr14-99679507;