dbSNP rs4987855: BCL2:c.*2309G>A (chr18-63126316-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.*2309G>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 220,572 control chromosomes in the GnomAD database, including 585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.059 ( 369 hom., cov: 32)

Exomes 𝑓: 0.071 ( 216 hom. )

Consequence

BCL2
NM_000633.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

38 publications found

Variant links:

COSMIC-nc: COSV61371341

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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.*2309G>A		3_prime_UTR	Exon 3 of 3	NP_000624.2	P10415-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCL2	ENST00000333681.5	TSL:1 MANE Select	c.*2309G>A	3_prime_UTR	Exon 3 of 3	ENSP00000329623.3	P10415-1
BCL2	ENST00000398117.1	TSL:1	c.*2309G>A	3_prime_UTR	Exon 2 of 2	ENSP00000381185.1	P10415-1
BCL2	ENST00000678301.1		c.*2309G>A	3_prime_UTR	Exon 2 of 2	ENSP00000504546.1	A0A7I2V5Q9

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9035

AN:

152014

Hom.:

369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0163

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0636

Gnomad ASJ

AF:

0.0668

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0225

Gnomad FIN

AF:

0.0475

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0928

Gnomad OTH

AF:

0.0770

GnomAD4 exome

AF:

0.0707

AC:

4841

AN:

68440

Hom.:

216

Cov.:

AF XY:

0.0709

AC XY:

2255

AN XY:

31804

show subpopulations

African (AFR)

AF:

0.0210

AC:

AN:

3148

American (AMR)

AF:

0.0510

AC:

105

AN:

2060

Ashkenazi Jewish (ASJ)

AF:

0.0616

AC:

268

AN:

4348

East Asian (EAS)

AF:

0.00129

AC:

AN:

10066

South Asian (SAS)

AF:

0.0149

AC:

AN:

604

European-Finnish (FIN)

AF:

0.0363

AC:

AN:

468

Middle Eastern (MID)

AF:

0.103

AC:

AN:

398

European-Non Finnish (NFE)

AF:

0.0934

AC:

3895

AN:

41684

Other (OTH)

AF:

0.0754

AC:

427

AN:

5664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

218

437

655

874

1092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

9037

AN:

152132

Hom.:

369

Cov.:

AF XY:

0.0570

AC XY:

4239

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0162

AC:

674

AN:

41496

American (AMR)

AF:

0.0635

AC:

970

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0668

AC:

232

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.0225

AC:

108

AN:

4804

European-Finnish (FIN)

AF:

0.0475

AC:

503

AN:

10582

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0928

AC:

6311

AN:

67994

Other (OTH)

AF:

0.0781

AC:

165

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

411

822

1234

1645

2056

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:

0.0803

Hom.:

1610

Bravo

AF:

0.0599

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.59

(source)

DANN

Benign

0.63

PhyloP100

-1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over