Variant 15-79971064-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004049.4(BCL2A1):c.56G>A(p.Cys19Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,632 control chromosomes in the GnomAD database, including 64,676 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.27 ( 6014 hom., cov: 33)

Exomes 𝑓: 0.28 ( 58662 hom. )

Consequence

BCL2A1
NM_004049.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

BCL2A1 (HGNC:991): (BCL2 related protein A1) This gene encodes a member of the BCL-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators that are involved in a wide variety of cellular activities such as embryonic development, homeostasis and tumorigenesis. The protein encoded by this gene is able to reduce the release of pro-apoptotic cytochrome c from mitochondria and block caspase activation. This gene is a direct transcription target of NF-kappa B in response to inflammatory mediators, and is up-regulated by different extracellular signals, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), CD40, phorbol ester and inflammatory cytokine TNF and IL-1, which suggests a cytoprotective function that is essential for lymphocyte activation as well as cell survival. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BCL2A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.9030386E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2A1	NM_004049.4 linkuse as main transcript	c.56G>A	p.Cys19Tyr	missense_variant	1/2	ENST00000267953.4	NP_004040.1	Q16548-1
BCL2A1	NM_001114735.2 linkuse as main transcript	c.56G>A	p.Cys19Tyr	missense_variant	1/3		NP_001108207.1	Q16548-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BCL2A1	ENST00000267953.4 linkuse as main transcript	c.56G>A	p.Cys19Tyr	missense_variant	1/2	1	NM_004049.4	ENSP00000267953.3	Q16548-1
BCL2A1	ENST00000335661.6 linkuse as main transcript	c.56G>A	p.Cys19Tyr	missense_variant	1/3	1		ENSP00000335250.6	Q16548-2
BCL2A1	ENST00000677151.1 linkuse as main transcript	c.56G>A	p.Cys19Tyr	missense_variant	1/1			ENSP00000504466.1	B4E1X9

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41653

AN:

151968

Hom.:

6011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.304

AC:

76401

AN:

251292

Hom.:

12842

AF XY:

0.305

AC XY:

41362

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.340

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.561

Gnomad SAS exome

AF:

0.405

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.279

GnomAD4 exome

AF:

0.275

AC:

402594

AN:

1461546

Hom.:

58662

Cov.:

AF XY:

0.279

AC XY:

202575

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.330

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.527

Gnomad4 SAS exome

AF:

0.402

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.274

AC:

41683

AN:

152086

Hom.:

6014

Cov.:

AF XY:

0.277

AC XY:

20611

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.280

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.550

Gnomad4 SAS

AF:

0.416

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.264

Hom.:

13733

Bravo

AF:

0.278

TwinsUK

AF:

0.257

AC:

954

ALSPAC

AF:

0.255

AC:

983

ESP6500AA

AF:

0.241

AC:

1063

ESP6500EA

AF:

0.257

AC:

2210

ExAC

AF:

0.303

AC:

36829

Asia WGS

AF:

0.433

AC:

1506

AN:

3478

EpiCase

AF:

0.254

EpiControl

AF:

0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

DANN

Benign

0.66

DEOGEN2

Benign

0.051

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.17

T;T

MetaRNN

Benign

0.000059

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.1

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

2.7

N;N

REVEL

Benign

0.056

Sift

Benign

0.74

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.016

MPC

0.85

ClinPred

0.0066

GERP RS

1.9

Varity_R

0.071

gMVP

0.49

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over