Variant 18-63318540-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000633.3(BCL2):c.127G>A(p.Ala43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 1,584,596 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0068 ( 51 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 450 hom. )

Consequence

BCL2
NM_000633.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0250

Variant links:

Genes affected

BCL2 (HGNC:990): (BCL2 apoptosis regulator) This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

BCL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017367601).

BP6

Variant 18-63318540-C-T is Benign according to our data. Variant chr18-63318540-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	2/3	ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	2/3	1	NM_000633.3	ENSP00000329623	P1	P10415-1

Frequencies

GnomAD3 genomes

AF:

0.00672

AC:

1022

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0895

Gnomad SAS

AF:

0.0865

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.0178

AC:

3838

AN:

215822

Hom.:

182

AF XY:

0.0206

AC XY:

2463

AN XY:

119746

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.000488

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0979

Gnomad SAS exome

AF:

0.0802

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000305

Gnomad OTH exome

AF:

0.00889

GnomAD4 exome

AF:

0.00714

AC:

10228

AN:

1432356

Hom.:

450

Cov.:

AF XY:

0.00929

AC XY:

6620

AN XY:

712880

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000556

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.0790

Gnomad4 FIN exome

AF:

0.0000210

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.00679

AC:

1033

AN:

152240

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0896

Gnomad4 SAS

AF:

0.0868

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00505

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.000248

AC:

ExAC

AF:

0.0178

AC:

2140

Asia WGS

AF:

0.0890

AC:

308

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

T;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.50

.;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.28

N;N;.

REVEL

Benign

0.064

Sift

Benign

0.69

T;T;.

Sift4G

Benign

0.67

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.018

MPC

0.85

ClinPred

0.0036

GERP RS

1.6

Varity_R

0.028

gMVP

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over