Variant chr12-12079387-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138723.2(BCL2L14):c.82G>A(p.Ala28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,614,072 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

BCL2L14
NM_138723.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.825

Variant links:

Genes affected

BCL2L14 (HGNC:16657): (BCL2 like 14) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Overexpression of this gene has been shown to induce apoptosis in cells. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported for this gene. [provided by RefSeq, May 2009]

BCL2L14 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=0.019772738).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L14	NM_138723.2 linkuse as main transcript	c.82G>A	p.Ala28Thr	missense_variant	2/6	ENST00000308721.9	NP_620049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L14	ENST00000308721.9 linkuse as main transcript	c.82G>A	p.Ala28Thr	missense_variant	2/6	1	NM_138723.2	ENSP00000309132	P1	Q9BZR8-1

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251478

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000287

AC:

419

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

218

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.000844

GnomAD4 genome

AF:

0.000526

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000366

Hom.:

Bravo

AF:

0.000706

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

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

Nov 12, 2021

The c.82G>A (p.A28T) alteration is located in exon 2 (coding exon 1) of the BCL2L14 gene. This alteration results from a G to A substitution at nucleotide position 82, causing the alanine (A) at amino acid position 28 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.012

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

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.26

M_CAP

Benign

0.0040

MetaRNN

Benign

0.020

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.;.;L;L;L;.

MutationTaster

Benign

0.98

N;N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.9

.;.;D;D;N;N;D;.

REVEL

Benign

0.023

Sift

Benign

0.23

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

Sift4G

Benign

0.16

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

Polyphen

0.55

P;.;.;.;P;P;B;.

Vest4

0.056

MVP

0.40

MPC

0.14

ClinPred

0.0060

GERP RS

2.3

Varity_R

0.042

gMVP

0.089

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