2-60493111-C-T

Position:

• chr2-60493111-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022893.4(BCL11A):​c.386-24278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,036 control chromosomes in the GnomAD database, including 32,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.63 (32265 hom., cov: 31)
• Consequence: BCL11A NM_022893.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:4
• Conservation: PhyloP100: -0.837

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-60493111-C-T is Benign according to our data. Variant chr2-60493111-C-T is described in ClinVar as [Benign]. Clinvar id is 127265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.386-24278G>A		intron_variant		ENST00000642384.2	NP_075044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL11A	ENST00000642384.2	c.386-24278G>A		intron_variant			NM_022893.4	ENSP00000496168

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96347 AN: 151918 Hom.: 32238 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.634 AC: 96415 AN: 152036 Hom.: 32265 Cov.: 31 AF XY: 0.619 AC XY: 45978 AN XY: 74310

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.0298

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.619

Alfa AF: 0.651 Hom.: 59534

Bravo AF: 0.624

Asia WGS AF: 0.282 AC: 984 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dias-Logan syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NG_011968.1(NM_018014.3):c.386-24278G>A in the BCL11A gene has an allele frequency of 0.713 in African subpopulation in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1. -

Fetal hemoglobin quantitative trait locus 5 Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Genomic Research Center, Shahid Beheshti University of Medical Sciences

-

- -

not specified Benign:1

Benign, criteria provided, single submitter

research

H3Africa Consortium

Oct 28, 2020

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.8, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.69

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: rs11886868; hg19: chr2-60720246;