dbSNP rs1473418: BCL2:c.-429G>C (chr18-63319316-C-G) – 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.-429G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 227,728 control chromosomes in the GnomAD database, including 110,918 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 0.98 ( 73507 hom., cov: 32)

Exomes 𝑓: 1.0 ( 37411 hom. )

Consequence

BCL2
NM_000633.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.834

Publications

7 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:

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3 link	c.-429G>C		5_prime_UTR_variant	Exon 1 of 3	ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5 link	c.-429G>C		5_prime_UTR_variant	Exon 1 of 3	1	NM_000633.3	ENSP00000329623.3
BCL2	ENST00000398117.1 link	c.-650G>C		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000381185.1

Frequencies

GnomAD3 genomes

AF:

0.982

AC:

149480

AN:

152192

Hom.:

73469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.939

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.985

GnomAD4 exome

AF:

0.996

AC:

75107

AN:

75418

Hom.:

37411

Cov.:

AF XY:

0.996

AC XY:

34593

AN XY:

34726

show subpopulations

African (AFR)

AF:

0.936

AC:

3324

AN:

3550

American (AMR)

AF:

0.993

AC:

2260

AN:

2276

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

4754

AN:

4754

East Asian (EAS)

AF:

1.00

AC:

10708

AN:

10708

South Asian (SAS)

AF:

1.00

AC:

644

AN:

644

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.987

AC:

470

AN:

476

European-Non Finnish (NFE)

AF:

1.00

AC:

46636

AN:

46656

Other (OTH)

AF:

0.993

AC:

6247

AN:

6290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<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:

0.982

AC:

149575

AN:

152310

Hom.:

73507

Cov.:

AF XY:

0.983

AC XY:

73191

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.938

AC:

38984

AN:

41548

American (AMR)

AF:

0.993

AC:

15202

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3471

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5190

AN:

5190

South Asian (SAS)

AF:

0.999

AC:

4823

AN:

4828

European-Finnish (FIN)

AF:

1.00

AC:

10611

AN:

10612

Middle Eastern (MID)

AF:

0.993

AC:

292

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68006

AN:

68030

Other (OTH)

AF:

0.985

AC:

2084

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

131

261

392

522

653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.993

Hom.:

4058

Bravo

AF:

0.979

Asia WGS

AF:

0.992

AC:

3452

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.4

(source)

DANN

Benign

0.55

PhyloP100

0.83

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=300/0

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