2-60452091-G-A

Variant names:

• chr2-60452091-G-A
• rs2058703
• ENST00000356842.9:c.*484C>T

Variant summary

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

The NM_001363864.1(BCL11A):​c.*474C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 227,174 control chromosomes in the GnomAD database, including 46,879 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 0.63 (30827 hom., cov: 33)
  • Exomes 𝑓: 0.64 (16052 hom.)
• Consequence: BCL11A NM_001363864.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363864.1. 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_001363864.1		c.*474C>T		3_prime_UTR	Exon 4 of 4	NP_001350793.1	A0A2U3TZJ5
	BCL11A	NM_018014.4		c.*484C>T		3_prime_UTR	Exon 5 of 5	NP_060484.2
	BCL11A	NM_138559.2		c.*474C>T		3_prime_UTR	Exon 5 of 5	NP_612569.1	Q9H165-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL11A	ENST00000356842.9	TSL:1	c.*484C>T		3_prime_UTR	Exon 5 of 5	ENSP00000349300.4	Q9H165-2
	BCL11A	ENST00000359629.10	TSL:1	c.*474C>T		3_prime_UTR	Exon 5 of 5	ENSP00000352648.5	Q9H165-3
	BCL11A	ENST00000489516.7	TSL:5	c.*474C>T		3_prime_UTR	Exon 5 of 5	ENSP00000488390.2	A0A0J9YXG2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95680 AN: 152008 Hom.: 30797 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.636 AC: 47723 AN: 75048 Hom.: 16052 Cov.: 0 AF XY: 0.631 AC XY: 21927 AN XY: 34730

African (AFR) AF: 0.672 AC: 2411 AN: 3586

American (AMR) AF: 0.749 AC: 1721 AN: 2298

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 2409 AN: 4740

East Asian (EAS) AF: 0.979 AC: 10409 AN: 10630

South Asian (SAS) AF: 0.552 AC: 369 AN: 668

European-Finnish (FIN) AF: 0.558 AC: 29 AN: 52

Middle Eastern (MID) AF: 0.467 AC: 212 AN: 454

European-Non Finnish (NFE) AF: 0.568 AC: 26308 AN: 46312

Other (OTH) AF: 0.611 AC: 3855 AN: 6308

GnomAD4 genome AF: 0.629 AC: 95762 AN: 152126 Hom.: 30827 Cov.: 33 AF XY: 0.630 AC XY: 46851 AN XY: 74358

African (AFR) AF: 0.679 AC: 28184 AN: 41496

American (AMR) AF: 0.711 AC: 10869 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1699 AN: 3468

East Asian (EAS) AF: 0.978 AC: 5069 AN: 5184

South Asian (SAS) AF: 0.568 AC: 2739 AN: 4826

European-Finnish (FIN) AF: 0.588 AC: 6200 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38989 AN: 67990

Other (OTH) AF: 0.610 AC: 1289 AN: 2112

Alfa AF: 0.594 Hom.: 44607

Bravo AF: 0.647

Asia WGS AF: 0.741 AC: 2576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.67
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2058703; hg19: chr2-60679226;