chr2-111123885-A-G

Position:

chr2-111123885-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138621.5(BCL2L11):c.140A>G(p.Asn47Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,609,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

BCL2L11
NM_138621.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.513

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027728587).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L11	NM_138621.5 linkuse as main transcript	c.140A>G	p.Asn47Ser	missense_variant	2/4	ENST00000393256.8	NP_619527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8 linkuse as main transcript	c.140A>G	p.Asn47Ser	missense_variant	2/4	1	NM_138621.5	ENSP00000376943	P1	O43521-1
MIR4435-2HG	ENST00000645030.2 linkuse as main transcript	n.453-86963T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000608

AC:

AN:

246606

Hom.:

AF XY:

0.0000450

AC XY:

AN XY:

133474

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000889

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.0000538

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000253

AC:

369

AN:

1456732

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

181

AN XY:

724712

show subpopulations

Gnomad4 AFR exome

AF:

0.0000904

Gnomad4 AMR exome

AF:

0.0000913

Gnomad4 ASJ exome

AF:

0.0000778

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000817

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000310

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.140A>G (p.N47S) alteration is located in exon 2 (coding exon 1) of the BCL2L11 gene. This alteration results from a A to G substitution at nucleotide position 140, causing the asparagine (N) at amino acid position 47 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.40

DANN

Benign

0.41

DEOGEN2

Benign

0.24

.;.;.;.;.;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.76

T;T;T;T;T;T;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.028

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;N;N;N;N;N;.

MutationTaster

Benign

1.0

D;D;D;D;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.11

N;.;.;.;.;.;N;N

REVEL

Benign

0.25

Sift

Benign

1.0

T;.;.;.;.;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T

Polyphen

0.0

.;.;.;B;.;.;B;.

Vest4

0.17, 0.24, 0.22, 0.20, 0.22, 0.22

MVP

0.068

MPC

0.039

ClinPred

0.0054

GERP RS

-0.76

Varity_R

0.045

gMVP

0.036

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over