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GeneBe

2-60460824-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_022893.4(BCL11A):c.2088T>C(p.Ser696=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,612,372 control chromosomes in the GnomAD database, including 352,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.72 ( 41375 hom., cov: 34)
Exomes 𝑓: 0.65 ( 311418 hom. )

Consequence

BCL11A
NM_022893.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.80
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-60460824-A-G is Benign according to our data. Variant chr2-60460824-A-G is described in ClinVar as [Benign]. Clinvar id is 1276488.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-60460824-A-G is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.8 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCL11ANM_022893.4 linkuse as main transcriptc.2088T>C p.Ser696= synonymous_variant 4/4 ENST00000642384.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCL11AENST00000642384.2 linkuse as main transcriptc.2088T>C p.Ser696= synonymous_variant 4/4 NM_022893.4 Q9H165-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.723
AC:
109908
AN:
152080
Hom.:
41311
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.906
Gnomad AMI
AF:
0.589
Gnomad AMR
AF:
0.767
Gnomad ASJ
AF:
0.560
Gnomad EAS
AF:
0.998
Gnomad SAS
AF:
0.757
Gnomad FIN
AF:
0.606
Gnomad MID
AF:
0.535
Gnomad NFE
AF:
0.607
Gnomad OTH
AF:
0.709
GnomAD3 exomes
AF:
0.702
AC:
174802
AN:
249048
Hom.:
63887
AF XY:
0.691
AC XY:
93387
AN XY:
135156
show subpopulations
Gnomad AFR exome
AF:
0.914
Gnomad AMR exome
AF:
0.850
Gnomad ASJ exome
AF:
0.562
Gnomad EAS exome
AF:
0.999
Gnomad SAS exome
AF:
0.734
Gnomad FIN exome
AF:
0.592
Gnomad NFE exome
AF:
0.606
Gnomad OTH exome
AF:
0.656
GnomAD4 exome
AF:
0.646
AC:
943971
AN:
1460174
Hom.:
311418
Cov.:
98
AF XY:
0.646
AC XY:
469550
AN XY:
726466
show subpopulations
Gnomad4 AFR exome
AF:
0.909
Gnomad4 AMR exome
AF:
0.839
Gnomad4 ASJ exome
AF:
0.567
Gnomad4 EAS exome
AF:
0.999
Gnomad4 SAS exome
AF:
0.727
Gnomad4 FIN exome
AF:
0.587
Gnomad4 NFE exome
AF:
0.616
Gnomad4 OTH exome
AF:
0.662
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.723
AC:
110027
AN:
152198
Hom.:
41375
Cov.:
34
AF XY:
0.724
AC XY:
53871
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.906
Gnomad4 AMR
AF:
0.768
Gnomad4 ASJ
AF:
0.560
Gnomad4 EAS
AF:
0.998
Gnomad4 SAS
AF:
0.755
Gnomad4 FIN
AF:
0.606
Gnomad4 NFE
AF:
0.607
Gnomad4 OTH
AF:
0.712
Alfa
AF:
0.625
Hom.:
30464
Bravo
AF:
0.745
Asia WGS
AF:
0.886
AC:
3079
AN:
3478
EpiCase
AF:
0.610
EpiControl
AF:
0.604

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 29, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
13
Dann
Benign
0.59

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7569946; hg19: chr2-60687959; COSMIC: COSV59626533; COSMIC: COSV59626533; API