2-60490908-T-G

Variant names:

• chr2-60490908-T-G
• rs1427407
• NM_022893.4:c.386-22075A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022893.4(BCL11A):​c.386-22075A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 151,946 control chromosomes in the GnomAD database, including 49,925 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 0.81 (49925 hom., cov: 30)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 111 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.838 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.386-22075A>C		intron	N/A	NP_075044.2
	BCL11A	NM_001405708.1		c.386-22075A>C		intron	N/A	NP_001392637.1	D9YZW0
	BCL11A	NM_001405709.1		c.386-22075A>C		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.386-22075A>C		intron	N/A	ENSP00000496168.1	Q9H165-1
	BCL11A	ENST00000335712.11	TSL:1	c.386-28484A>C		intron	N/A	ENSP00000338774.7	Q9H165-6
	BCL11A	ENST00000358510.6	TSL:1	c.386-28484A>C		intron	N/A	ENSP00000351307.5	A0A2U3TZJ5

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122819 AN: 151830 Hom.: 49883 Cov.: 30

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.809 AC: 122917 AN: 151946 Hom.: 49925 Cov.: 30 AF XY: 0.808 AC XY: 60007 AN XY: 74252

African (AFR) AF: 0.765 AC: 31670 AN: 41390

American (AMR) AF: 0.788 AC: 12048 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2488 AN: 3470

East Asian (EAS) AF: 0.786 AC: 4068 AN: 5174

South Asian (SAS) AF: 0.859 AC: 4122 AN: 4796

European-Finnish (FIN) AF: 0.848 AC: 8944 AN: 10552

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.839 AC: 57006 AN: 67978

Other (OTH) AF: 0.797 AC: 1675 AN: 2102

Alfa AF: 0.825 Hom.: 203883

Bravo AF: 0.802

Asia WGS AF: 0.832 AC: 2890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Benign	0.85
PhyloP100		2.7
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: rs1427407; hg19: chr2-60718043;