rs7557939

Positions:

• chr2-60494212-G-A

Variant summary

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

The NM_022893.4(BCL11A):​c.386-25379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,990 control chromosomes in the GnomAD database, including 32,029 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 0.63 (32029 hom., cov: 31)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-25379C>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.386-25379C>T		intron_variant			NM_022893.4	ENSP00000496168

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96005 AN: 151872 Hom.: 32010 Cov.: 31

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.632 AC: 96063 AN: 151990 Hom.: 32029 Cov.: 31 AF XY: 0.617 AC XY: 45844 AN XY: 74322

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.0300

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.618

Alfa AF: 0.649 Hom.: 10289

Bravo AF: 0.622

Asia WGS AF: 0.285 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.53

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: rs7557939; hg19: chr2-60721347;