rs2556377

chr2-60533502-G-Achr2-60533502-G-Cchr2-60533502-G-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+12469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,200 control chromosomes in the GnomAD database, including 48,708 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 (48704 hom., cov: 32)
  • Exomes 𝑓: 0.69 (4 hom.)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL11A	NM_022893.4	c.385+12469C>T		intron_variant		ENST00000642384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL11A	ENST00000642384.2	c.385+12469C>T		intron_variant			NM_022893.4

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121395 AN: 152066 Hom.: 48656 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.688 AC: 11 AN: 16 Hom.: 4 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.798 AC: 121502 AN: 152184 Hom.: 48704 Cov.: 32 AF XY: 0.795 AC XY: 59129 AN XY: 74400

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.800

Alfa AF: 0.817 Hom.: 42954

Bravo AF: 0.795

Asia WGS AF: 0.805 AC: 2796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	8.5
Dann	Benign	0.93

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: rs2556377; hg19: chr2-60760637;