rs11886868

Variant names:

• chr2-60493111-C-T
• rs11886868
• NM_022893.4:c.386-24278G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022893.4(BCL11A):​c.386-24278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,036 control chromosomes in the GnomAD database, including 32,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.63 (32265 hom., cov: 31)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:5
• Conservation: PhyloP100: -0.837
• Publications: 92 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-60493111-C-T is Benign according to our data. Variant chr2-60493111-C-T is described in ClinVar as Benign. ClinVar VariationId is 127265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 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.386-24278G>A		intron	N/A	NP_075044.2
	BCL11A	NM_001405708.1		c.386-24278G>A		intron	N/A	NP_001392637.1	D9YZW0
	BCL11A	NM_001405709.1		c.386-24278G>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.386-24278G>A		intron	N/A	ENSP00000496168.1	Q9H165-1
	BCL11A	ENST00000335712.11	TSL:1	c.386-30687G>A		intron	N/A	ENSP00000338774.7	Q9H165-6
	BCL11A	ENST00000358510.6	TSL:1	c.386-30687G>A		intron	N/A	ENSP00000351307.5	A0A2U3TZJ5

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96347 AN: 151918 Hom.: 32238 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.634 AC: 96415 AN: 152036 Hom.: 32265 Cov.: 31 AF XY: 0.619 AC XY: 45978 AN XY: 74310

African (AFR) AF: 0.712 AC: 29501 AN: 41462

American (AMR) AF: 0.488 AC: 7468 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1979 AN: 3470

East Asian (EAS) AF: 0.0298 AC: 154 AN: 5174

South Asian (SAS) AF: 0.415 AC: 1999 AN: 4820

European-Finnish (FIN) AF: 0.608 AC: 6415 AN: 10546

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.690 AC: 46898 AN: 67964

Other (OTH) AF: 0.619 AC: 1307 AN: 2110

Alfa AF: 0.653 Hom.: 130696

Bravo AF: 0.624

Asia WGS AF: 0.282 AC: 984 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Dias-Logan syndrome (3)
1	-	-	Fetal hemoglobin quantitative trait locus 5 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.84
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: rs11886868; hg19: chr2-60720246;