2-60498316-G-C

Position:

• chr2-60498316-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022893.4(BCL11A):​c.386-29483C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,546 control chromosomes in the GnomAD database, including 12,021 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 0.39 (12021 hom., cov: 30)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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]

ENSG00000233953 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-29483C>G		intron_variant		ENST00000642384.2	NP_075044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL11A	ENST00000642384.2	c.386-29483C>G		intron_variant			NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58521 AN: 151430 Hom.: 12001 Cov.: 30

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.387 AC: 58584 AN: 151546 Hom.: 12021 Cov.: 30 AF XY: 0.375 AC XY: 27762 AN XY: 74010

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.375

Alfa AF: 0.270 Hom.: 644

Bravo AF: 0.381

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs7606173; hg19: chr2-60725451;