Genetic Variant NM_000633.3:c.*1937A>G (chr18-63126688-T-C) – 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.*1937A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 226,854 control chromosomes in the GnomAD database, including 416 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 0.049 ( 292 hom., cov: 33)

Exomes 𝑓: 0.050 ( 124 hom. )

Consequence

BCL2
NM_000633.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.555

Publications

37 publications found

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:

ENSG00000299452 (HGNC:):

ENSG00000299452 links:

Genome browser will be placed here

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=-0.73).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3 link	c.*1937A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000333681.5	NP_000624.2	P10415-1A0A024R2B3
BCL2	XM_047437733.1 link	c.*1937A>G		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.*1937A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_000633.3	ENSP00000329623.3		P10415-1

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7512

AN:

152134

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0448

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0668

Gnomad OTH

AF:

0.0454

GnomAD4 exome

AF:

0.0495

AC:

3694

AN:

74602

Hom.:

124

Cov.:

AF XY:

0.0503

AC XY:

1732

AN XY:

34446

show subpopulations

African (AFR)

AF:

0.00868

AC:

AN:

3570

American (AMR)

AF:

0.0290

AC:

AN:

2272

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

232

AN:

4706

East Asian (EAS)

AF:

0.000659

AC:

AN:

10624

South Asian (SAS)

AF:

0.0140

AC:

AN:

644

European-Finnish (FIN)

AF:

0.0833

AC:

AN:

Middle Eastern (MID)

AF:

0.0149

AC:

AN:

470

European-Non Finnish (NFE)

AF:

0.0656

AC:

3018

AN:

46018

Other (OTH)

AF:

0.0512

AC:

320

AN:

6250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

178

356

534

712

890

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:

0.0493

AC:

7512

AN:

152252

Hom.:

292

Cov.:

AF XY:

0.0518

AC XY:

3854

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0123

AC:

512

AN:

41548

American (AMR)

AF:

0.0448

AC:

685

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5188

South Asian (SAS)

AF:

0.0153

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.129

AC:

1363

AN:

10580

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0668

AC:

4546

AN:

68018

Other (OTH)

AF:

0.0449

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

351

702

1054

1405

1756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0569

Hom.:

973

Bravo

AF:

0.0400

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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