rs7557939

Variant names:

• chr2-60494212-G-A
• rs7557939
• NM_022893.4:c.386-25379C>T

Variant summary

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

The NM_022893.4(BCL11A):​c.386-25379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,990 control chromosomes in the GnomAD database, including 32,029 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 (32029 hom., cov: 31)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 26 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 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.386-25379C>T		intron	N/A	NP_075044.2
	BCL11A	NM_001405708.1		c.386-25379C>T		intron	N/A	NP_001392637.1	D9YZW0
	BCL11A	NM_001405709.1		c.386-25379C>T		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.386-25379C>T		intron	N/A	ENSP00000496168.1	Q9H165-1
	BCL11A	ENST00000335712.11	TSL:1	c.386-31788C>T		intron	N/A	ENSP00000338774.7	Q9H165-6
	BCL11A	ENST00000358510.6	TSL:1	c.386-31788C>T		intron	N/A	ENSP00000351307.5	A0A2U3TZJ5

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96005 AN: 151872 Hom.: 32010 Cov.: 31

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.632 AC: 96063 AN: 151990 Hom.: 32029 Cov.: 31 AF XY: 0.617 AC XY: 45844 AN XY: 74322

African (AFR) AF: 0.703 AC: 29131 AN: 41438

American (AMR) AF: 0.487 AC: 7443 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3470

East Asian (EAS) AF: 0.0300 AC: 155 AN: 5170

South Asian (SAS) AF: 0.419 AC: 2017 AN: 4814

European-Finnish (FIN) AF: 0.607 AC: 6420 AN: 10576

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46919 AN: 67942

Other (OTH) AF: 0.618 AC: 1301 AN: 2104

Alfa AF: 0.652 Hom.: 61463

Bravo AF: 0.622

Asia WGS AF: 0.285 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.53
PhyloP100		-0.025
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: rs7557939; hg19: chr2-60721347;