2-60481462-C-T

Variant names:

• chr2-60481462-C-T
• rs6732518
• NM_022893.4:c.386-12629G>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.386-12629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,744 control chromosomes in the GnomAD database, including 31,062 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 0.62 (31062 hom., cov: 30)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 17 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-12629G>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.386-12629G>A		intron_variant	Intron 2 of 3		NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94626 AN: 151626 Hom.: 31043 Cov.: 30

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.0305

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.624 AC: 94676 AN: 151744 Hom.: 31062 Cov.: 30 AF XY: 0.609 AC XY: 45156 AN XY: 74108

African (AFR) AF: 0.683 AC: 28193 AN: 41274

American (AMR) AF: 0.486 AC: 7415 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2013 AN: 3466

East Asian (EAS) AF: 0.0303 AC: 157 AN: 5176

South Asian (SAS) AF: 0.412 AC: 1978 AN: 4802

European-Finnish (FIN) AF: 0.615 AC: 6468 AN: 10520

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46442 AN: 67938

Other (OTH) AF: 0.608 AC: 1280 AN: 2106

Alfa AF: 0.648 Hom.: 70231

Bravo AF: 0.614

Asia WGS AF: 0.275 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.68
PhyloP100		1.4
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: rs6732518; hg19: chr2-60708597; COSMIC: COSV59626346;