Genetic Variant NM_000633.3:c.*2364G>A (chr18-63126261-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000633.3(BCL2):c.*2364G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 220,032 control chromosomes in the GnomAD database, including 580 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.059 ( 367 hom., cov: 32)

Exomes 𝑓: 0.071 ( 213 hom. )

Consequence

BCL2
NM_000633.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0540

Publications

22 publications found

Variant links:

COSMIC-nc: COSV61371332

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:

ENSG00000299452 (HGNC:):

ENSG00000299452 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3 link	c.*2364G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000333681.5	NP_000624.2	P10415-1A0A024R2B3
BCL2	XM_047437733.1 link	c.*2364G>A		3_prime_UTR_variant	Exon 2 of 2		XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5 link	c.*2364G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_000633.3	ENSP00000329623.3		P10415-1

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9041

AN:

151994

Hom.:

367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0636

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0227

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0928

Gnomad OTH

AF:

0.0770

GnomAD4 exome

AF:

0.0706

AC:

4794

AN:

67920

Hom.:

213

Cov.:

AF XY:

0.0711

AC XY:

2241

AN XY:

31532

show subpopulations

African (AFR)

AF:

0.0213

AC:

AN:

3096

American (AMR)

AF:

0.0517

AC:

106

AN:

2052

Ashkenazi Jewish (ASJ)

AF:

0.0644

AC:

278

AN:

4314

East Asian (EAS)

AF:

0.000901

AC:

AN:

9986

South Asian (SAS)

AF:

0.0136

AC:

AN:

588

European-Finnish (FIN)

AF:

0.0366

AC:

AN:

464

Middle Eastern (MID)

AF:

0.0990

AC:

AN:

404

European-Non Finnish (NFE)

AF:

0.0932

AC:

3856

AN:

41364

Other (OTH)

AF:

0.0732

AC:

414

AN:

5652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

208

417

625

834

1042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0594

AC:

9043

AN:

152112

Hom.:

367

Cov.:

AF XY:

0.0570

AC XY:

4241

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0165

AC:

684

AN:

41486

American (AMR)

AF:

0.0635

AC:

971

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

230

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0227

AC:

109

AN:

4804

European-Finnish (FIN)

AF:

0.0477

AC:

505

AN:

10596

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0928

AC:

6305

AN:

67978

Other (OTH)

AF:

0.0781

AC:

165

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

433

866

1299

1732

2165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0555

Hom.:

106

Bravo

AF:

0.0599

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.7

(source)

DANN

Benign

0.73

PhyloP100

-0.054

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over