Variant 19-49667113-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138639.2(BCL2L12):c.202C>T(p.Pro68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,614,042 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 15 hom. )

Consequence

BCL2L12
NM_138639.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.472

Variant links:

Genes affected

BCL2L12 (HGNC:13787): (BCL2 like 12) This gene encodes a member of a family of proteins containing a Bcl-2 homology domain 2 (BH2). The encoded protein is an anti-apoptotic factor that acts as an inhibitor of caspases 3 and 7 in the cytoplasm. In the nucleus, it binds to the p53 tumor suppressor protein, preventing its association with target genes. Overexpression of this gene has been detected in a number of different cancers. There is a pseudogene for this gene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

BCL2L12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061015785).

BP6

Variant 19-49667113-C-T is Benign according to our data. Variant chr19-49667113-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3387907.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L12	NM_138639.2 link	c.202C>T	p.Pro68Ser	missense_variant	3/7	ENST00000246784.8	NP_619580.2	Q9HB09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L12	ENST00000246784.8 link	c.202C>T	p.Pro68Ser	missense_variant	3/7	1	NM_138639.2	ENSP00000246784.4		A0A087WSV0

Frequencies

GnomAD3 genomes

AF:

0.00302

AC:

459

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00470

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00318

AC:

800

AN:

251390

Hom.:

AF XY:

0.00326

AC XY:

443

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00506

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00541

Gnomad NFE exome

AF:

0.00435

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00346

AC:

5063

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

2538

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00482

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.00598

Gnomad4 NFE exome

AF:

0.00373

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

AF:

0.00301

AC:

459

AN:

152248

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.00470

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00381

Hom.:

Bravo

AF:

0.00269

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00307

AC:

373

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00567

EpiControl

AF:

0.00528

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

BCL2L12: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.036

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

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.83

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

M_CAP

Benign

0.0068

MetaRNN

Benign

0.0061

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

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

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.3

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

REVEL

Benign

0.036

Sift

Benign

0.47

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

Sift4G

Benign

0.26

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

Polyphen

0.026

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

Vest4

0.16

MVP

0.38

MPC

0.23

ClinPred

0.0077

GERP RS

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.26

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.

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