2-60493816-A-G

Position:

• chr2-60493816-A-G

Variant summary

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

The NM_022893.4(BCL11A):​c.386-24983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,048 control chromosomes in the GnomAD database, including 49,520 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 (49520 hom., cov: 30)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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]

BCL11A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-24983T>C		intron_variant		ENST00000642384.2	NP_075044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL11A	ENST00000642384.2	c.386-24983T>C		intron_variant			NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122256 AN: 151930 Hom.: 49483 Cov.: 30

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.805 AC: 122349 AN: 152048 Hom.: 49520 Cov.: 30 AF XY: 0.803 AC XY: 59694 AN XY: 74322

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.799

Alfa AF: 0.799 Hom.: 3415

Bravo AF: 0.797

Asia WGS AF: 0.828 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.016
DANN	Benign	0.52

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: rs4671393; hg19: chr2-60720951;