Variant 22-17689013-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015367.4(BCL2L13):c.257A>G(p.His86Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 1,613,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

BCL2L13
NM_015367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53

Variant links:

Genes affected

BCL2L13 (HGNC:17164): (BCL2 like 13) This gene encodes a mitochondrially-localized protein with conserved B-cell lymphoma 2 homology motifs. Overexpression of the encoded protein results in apoptosis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

BCL2L13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16484159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L13	NM_015367.4 linkuse as main transcript	c.257A>G	p.His86Arg	missense_variant	4/7	ENST00000317582.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L13	ENST00000317582.10 linkuse as main transcript	c.257A>G	p.His86Arg	missense_variant	4/7	1	NM_015367.4	A2	Q9BXK5-1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000314

AC:

AN:

251216

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000528

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000303

AC:

443

AN:

1461710

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

209

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000354

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000296

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000501

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000889

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

Sep 01, 2021

The c.257A>G (p.H86R) alteration is located in exon 4 (coding exon 3) of the BCL2L13 gene. This alteration results from a A to G substitution at nucleotide position 257, causing the histidine (H) at amino acid position 86 to be replaced by an arginine (R). 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

0.21

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.0098

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.;.;M;M;.

MutationTaster

Benign

0.99

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-4.1

D;.;.;D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.014

D;.;.;D;D;D

Sift4G

Uncertain

0.041

D;T;D;D;D;D

Polyphen

1.0

D;.;.;B;D;D

Vest4

0.45

MVP

0.25

MPC

0.36

ClinPred

0.098

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.30

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