2-60494905-C-T

Variant names:

• chr2-60494905-C-T
• rs6706648
• NM_022893.4:c.386-26072G>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.386-26072G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,888 control chromosomes in the GnomAD database, including 7,805 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 0.31 (7805 hom., cov: 32)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484
• Publications: 23 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-26072G>A		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.386-26072G>A		intron_variant	Intron 2 of 3		NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46923 AN: 151770 Hom.: 7789 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.309 AC: 46984 AN: 151888 Hom.: 7805 Cov.: 32 AF XY: 0.300 AC XY: 22294 AN XY: 74246

African (AFR) AF: 0.398 AC: 16461 AN: 41354

American (AMR) AF: 0.225 AC: 3432 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 876 AN: 3468

East Asian (EAS) AF: 0.0101 AC: 52 AN: 5174

South Asian (SAS) AF: 0.158 AC: 757 AN: 4800

European-Finnish (FIN) AF: 0.303 AC: 3196 AN: 10548

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.313 AC: 21288 AN: 67968

Other (OTH) AF: 0.277 AC: 584 AN: 2110

Alfa AF: 0.304 Hom.: 26472

Bravo AF: 0.304

Asia WGS AF: 0.101 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.39
PhyloP100		0.48
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: rs6706648; hg19: chr2-60722040;