Genetic Variant NM_138621.5:c.-14+650A>G (chr2-111121838-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138621.5(BCL2L11):c.-14+650A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,092 control chromosomes in the GnomAD database, including 14,766 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 0.43 ( 14766 hom., cov: 33)

Consequence

BCL2L11
NM_138621.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

10 publications found

Variant links:

Genes affected

BCL2L11 (HGNC:994): (BCL2 like 11) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]

BCL2L11 links:

ENSG00000293584 (HGNC:):

ENSG00000293584 links:

MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

MIR4435-2HG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L11	NM_138621.5 link	c.-14+650A>G		intron_variant	Intron 1 of 3	ENST00000393256.8	NP_619527.1	O43521-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8 link	c.-14+650A>G		intron_variant	Intron 1 of 3	1	NM_138621.5	ENSP00000376943.2		O43521-1
ENSG00000293584	ENST00000715207.1 link	c.36+650A>G		intron_variant	Intron 1 of 1			ENSP00000520414.1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65923

AN:

151976

Hom.:

14766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.392

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

GnomAD4 genome

AF:

0.434

AC:

65941

AN:

152092

Hom.:

14766

Cov.:

AF XY:

0.428

AC XY:

31798

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.427

AC:

17716

AN:

41492

American (AMR)

AF:

0.296

AC:

4532

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1273

AN:

3466

East Asian (EAS)

AF:

0.430

AC:

2217

AN:

5152

South Asian (SAS)

AF:

0.226

AC:

1092

AN:

4826

European-Finnish (FIN)

AF:

0.511

AC:

5400

AN:

10572

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.477

AC:

32408

AN:

67966

Other (OTH)

AF:

0.394

AC:

833

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1944

3887

5831

7774

9718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.468

Hom.:

2130

Bravo

AF:

0.422

Asia WGS

AF:

0.321

AC:

1117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.4

(source)

DANN

Benign

0.70

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over