dbSNP rs1041372390: BCL2L11:p.Arg14Arg (chr2-111123785-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_138621.5(BCL2L11):c.40C>A(p.Arg14Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,296,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

BCL2L11
NM_138621.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Publications

0 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:

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

MIR4435-2HG links:

ENSG00000293584 (HGNC:):

ENSG00000293584 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=-0.048 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL2L11	NM_138621.5	MANE Select	c.40C>A	p.Arg14Arg	synonymous	Exon 2 of 4	NP_619527.1	O43521-1
BCL2L11	NM_001204108.1		c.40C>A	p.Arg14Arg	synonymous	Exon 2 of 5	NP_001191037.1	O43521-8
BCL2L11	NM_138622.4		c.40C>A	p.Arg14Arg	synonymous	Exon 2 of 5	NP_619528.1	O43521-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL2L11	ENST00000393256.8	TSL:1 MANE Select	c.40C>A	p.Arg14Arg	synonymous	Exon 2 of 4	ENSP00000376943.2	O43521-1
BCL2L11	ENST00000405953.6	TSL:1	c.40C>A	p.Arg14Arg	synonymous	Exon 2 of 4	ENSP00000384641.1	O43521-17
BCL2L11	ENST00000361493.10	TSL:1	n.40C>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000354879.6	A0A0C4DH20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000154

AC:

AN:

1296708

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

631280

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28288

American (AMR)

AF:

0.00

AC:

AN:

23800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18224

East Asian (EAS)

AF:

0.00

AC:

AN:

35206

South Asian (SAS)

AF:

0.00

AC:

AN:

57432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5102

European-Non Finnish (NFE)

AF:

0.00000195

AC:

AN:

1028216

Other (OTH)

AF:

0.00

AC:

AN:

52926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.9

(source)

DANN

Benign

0.63

PhyloP100

-0.048

PromoterAI

-0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over