dbSNP rs4987843: BCL2:c.*317G>A (chr18-63128308-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.*317G>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 0.132 in 262,416 control chromosomes in the GnomAD database, including 3,171 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 0.15 ( 2375 hom., cov: 33)

Exomes 𝑓: 0.10 ( 796 hom. )

Consequence

BCL2
NM_000633.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Publications

12 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 (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3 link	c.*317G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000333681.5	NP_000624.2	P10415-1A0A024R2B3
BCL2	XM_047437733.1 link	c.*317G>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.*317G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_000633.3	ENSP00000329623.3		P10415-1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23207

AN:

152134

Hom.:

2365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0584

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.103

AC:

11341

AN:

110164

Hom.:

796

Cov.:

AF XY:

0.102

AC XY:

5399

AN XY:

53140

show subpopulations

African (AFR)

AF:

0.293

AC:

1318

AN:

4504

American (AMR)

AF:

0.0972

AC:

352

AN:

3622

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

761

AN:

5946

East Asian (EAS)

AF:

0.00150

AC:

AN:

12692

South Asian (SAS)

AF:

0.0518

AC:

200

AN:

3860

European-Finnish (FIN)

AF:

0.0775

AC:

167

AN:

2154

Middle Eastern (MID)

AF:

0.179

AC:

109

AN:

610

European-Non Finnish (NFE)

AF:

0.106

AC:

7269

AN:

68482

Other (OTH)

AF:

0.138

AC:

1146

AN:

8294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

502

1003

1505

2006

2508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.153

AC:

23235

AN:

152252

Hom.:

2375

Cov.:

AF XY:

0.147

AC XY:

10954

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.298

AC:

12354

AN:

41516

American (AMR)

AF:

0.113

AC:

1729

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

495

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.0580

AC:

280

AN:

4826

European-Finnish (FIN)

AF:

0.0867

AC:

920

AN:

10608

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6953

AN:

68016

Other (OTH)

AF:

0.168

AC:

355

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

972

1944

2917

3889

4861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.127

Hom.:

2086

Bravo

AF:

0.163

Asia WGS

AF:

0.0460

AC:

160

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

1.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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