NM_022893.4:c.386-17267T>C

Variant names:

• chr2-60486100-A-G
• rs10189857
• NM_022893.4:c.386-17267T>C

Variant summary

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

The NM_022893.4(BCL11A):​c.386-17267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,030 control chromosomes in the GnomAD database, including 14,746 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 0.43 (14746 hom., cov: 32)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716
• Publications: 55 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Ambry Genetics, G2P, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-17267T>C		intron_variant	Intron 2 of 3	ENST00000642384.2	NP_075044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL11A	ENST00000642384.2	c.386-17267T>C		intron_variant	Intron 2 of 3		NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64953 AN: 151912 Hom.: 14732 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.427 AC: 64985 AN: 152030 Hom.: 14746 Cov.: 32 AF XY: 0.438 AC XY: 32533 AN XY: 74326

African (AFR) AF: 0.322 AC: 13358 AN: 41456

American (AMR) AF: 0.488 AC: 7451 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3470

East Asian (EAS) AF: 0.774 AC: 4002 AN: 5170

South Asian (SAS) AF: 0.672 AC: 3240 AN: 4824

European-Finnish (FIN) AF: 0.474 AC: 4999 AN: 10556

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29231 AN: 67962

Other (OTH) AF: 0.429 AC: 907 AN: 2112

Alfa AF: 0.433 Hom.: 64284

Bravo AF: 0.425

Asia WGS AF: 0.710 AC: 2466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		0.72
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: rs10189857; hg19: chr2-60713235;