2-60477798-A-T

Variant names:

• chr2-60477798-A-T
• rs7593947
• NM_022893.4:c.386-8965T>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.386-8965T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,676 control chromosomes in the GnomAD database, including 26,776 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 0.58 (26776 hom., cov: 29)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-8965T>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.386-8965T>A		intron_variant	Intron 2 of 3		NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87956 AN: 151558 Hom.: 26733 Cov.: 29

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.581 AC: 88062 AN: 151676 Hom.: 26776 Cov.: 29 AF XY: 0.588 AC XY: 43544 AN XY: 74116

African (AFR) AF: 0.742 AC: 30672 AN: 41352

American (AMR) AF: 0.580 AC: 8851 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1519 AN: 3468

East Asian (EAS) AF: 0.747 AC: 3823 AN: 5118

South Asian (SAS) AF: 0.740 AC: 3549 AN: 4796

European-Finnish (FIN) AF: 0.518 AC: 5440 AN: 10500

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32633 AN: 67880

Other (OTH) AF: 0.541 AC: 1141 AN: 2108

Alfa AF: 0.529 Hom.: 2606

Bravo AF: 0.590

Asia WGS AF: 0.764 AC: 2657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		-0.22
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: rs7593947; hg19: chr2-60704933;