rs6738440

Variant names:

• chr2-60495106-A-G
• rs6738440
• NM_022893.4:c.386-26273T>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.386-26273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,102 control chromosomes in the GnomAD database, including 5,212 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 0.25 (5212 hom., cov: 32)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-26273T>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.386-26273T>C		intron_variant	Intron 2 of 3		NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38652 AN: 151984 Hom.: 5203 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.254 AC: 38688 AN: 152102 Hom.: 5212 Cov.: 32 AF XY: 0.246 AC XY: 18256 AN XY: 74352

African (AFR) AF: 0.282 AC: 11701 AN: 41478

American (AMR) AF: 0.196 AC: 3000 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3468

East Asian (EAS) AF: 0.00850 AC: 44 AN: 5178

South Asian (SAS) AF: 0.118 AC: 569 AN: 4830

European-Finnish (FIN) AF: 0.262 AC: 2773 AN: 10584

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19066 AN: 67954

Other (OTH) AF: 0.238 AC: 503 AN: 2110

Alfa AF: 0.263 Hom.: 12390

Bravo AF: 0.250

Asia WGS AF: 0.0800 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.53
PhyloP100		-0.024
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: rs6738440; hg19: chr2-60722241;