rs2556376

Positions:

• chr2-60532897-C-A
• chr2-60532897-C-G
• chr2-60532897-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022893.4(BCL11A):​c.385+13074G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,128 control chromosomes in the GnomAD database, including 49,229 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 0.80 (49229 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651

Genes affected

BCL11A (HGNC:13221): (BCL11 transcription factor A) This gene encodes a C2H2 type zinc-finger protein by its similarity to the mouse Bcl11a/Evi9 protein. The corresponding mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.385+13074G>T		intron_variant		ENST00000642384.2	NP_075044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL11A	ENST00000642384.2	c.385+13074G>T		intron_variant			NM_022893.4	ENSP00000496168

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122023 AN: 152010 Hom.: 49182 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.801

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.803 AC: 122129 AN: 152128 Hom.: 49229 Cov.: 32 AF XY: 0.799 AC XY: 59432 AN XY: 74376

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.803

Alfa AF: 0.827 Hom.: 50542

Bravo AF: 0.799

Asia WGS AF: 0.806 AC: 2801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.74

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: rs2556376; hg19: chr2-60760032;