2-60491212-C-T

Variant names:

• chr2-60491212-C-T
• rs7599488
• NM_022893.4:c.386-22379G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022893.4(BCL11A):​c.386-22379G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,094 control chromosomes in the GnomAD database, including 14,519 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 0.42 (14519 hom., cov: 32)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 41 publications found

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 Gene-Disease associations (from GenCC):

• Dias-Logan syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022893.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL11A	NM_022893.4	MANE Select	c.386-22379G>A		intron	N/A	NP_075044.2
	BCL11A	NM_001405708.1		c.386-22379G>A		intron	N/A	NP_001392637.1	D9YZW0
	BCL11A	NM_001405709.1		c.386-22379G>A		intron	N/A	NP_001392638.1	D9YZW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL11A	ENST00000642384.2	MANE Select	c.386-22379G>A		intron	N/A	ENSP00000496168.1	Q9H165-1
	BCL11A	ENST00000335712.11	TSL:1	c.386-28788G>A		intron	N/A	ENSP00000338774.7	Q9H165-6
	BCL11A	ENST00000358510.6	TSL:1	c.386-28788G>A		intron	N/A	ENSP00000351307.5	A0A2U3TZJ5

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64350 AN: 151976 Hom.: 14505 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.423 AC: 64383 AN: 152094 Hom.: 14519 Cov.: 32 AF XY: 0.433 AC XY: 32221 AN XY: 74344

African (AFR) AF: 0.316 AC: 13122 AN: 41468

American (AMR) AF: 0.482 AC: 7376 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3466

East Asian (EAS) AF: 0.771 AC: 3994 AN: 5178

South Asian (SAS) AF: 0.666 AC: 3215 AN: 4824

European-Finnish (FIN) AF: 0.474 AC: 5007 AN: 10572

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29005 AN: 67982

Other (OTH) AF: 0.424 AC: 894 AN: 2110

Alfa AF: 0.429 Hom.: 25490

Bravo AF: 0.421

Asia WGS AF: 0.704 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.76
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7599488; hg19: chr2-60718347;