dbSNP rs3810294: BBC3:c.-15-126G>A (chr19-47228572-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_014417.5(BBC3):c.-15-126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 980,766 control chromosomes in the GnomAD database, including 8,462 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 0.14 ( 1650 hom., cov: 31)

Exomes 𝑓: 0.13 ( 6812 hom. )

Consequence

BBC3
NM_014417.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

5 publications found

Variant links:

Genes affected

BBC3 (HGNC:17868): (BCL2 binding component 3) This gene encodes a member of the BCL-2 family of proteins. This family member belongs to the BH3-only pro-apoptotic subclass. The protein cooperates with direct activator proteins to induce mitochondrial outer membrane permeabilization and apoptosis. It can bind to anti-apoptotic Bcl-2 family members to induce mitochondrial dysfunction and caspase activation. Because of its pro-apoptotic role, this gene is a potential drug target for cancer therapy and for tissue injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

BBC3 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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBC3	NM_014417.5 link	c.-15-126G>A		intron_variant	Intron 1 of 3	ENST00000439096.3	NP_055232.1	Q9BXH1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BBC3	ENST00000439096.3 link	c.-15-126G>A	intron_variant	Intron 1 of 3	1	NM_014417.5	ENSP00000395862.2	Q9BXH1-1
BBC3	ENST00000449228.5 link	c.89-126G>A	intron_variant	Intron 1 of 3	1		ENSP00000404503.1	Q96PG8-2
BBC3	ENST00000341983.8 link	c.89-1818G>A	intron_variant	Intron 1 of 2	1		ENSP00000341155.4	Q9BXH1-2
BBC3	ENST00000300880.11 link	c.88+3943G>A	intron_variant	Intron 1 of 1	1		ENSP00000300880.7	Q96PG8-1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21246

AN:

151822

Hom.:

1651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.0946

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0591

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.128

AC:

105713

AN:

828826

Hom.:

6812

AF XY:

0.126

AC XY:

50016

AN XY:

396222

show subpopulations

African (AFR)

AF:

0.166

AC:

2928

AN:

17678

American (AMR)

AF:

0.193

AC:

1510

AN:

7828

Ashkenazi Jewish (ASJ)

AF:

0.0883

AC:

1099

AN:

12452

East Asian (EAS)

AF:

0.145

AC:

3597

AN:

24782

South Asian (SAS)

AF:

0.0663

AC:

917

AN:

13838

European-Finnish (FIN)

AF:

0.106

AC:

2212

AN:

20904

Middle Eastern (MID)

AF:

0.118

AC:

287

AN:

2430

European-Non Finnish (NFE)

AF:

0.128

AC:

88897

AN:

693856

Other (OTH)

AF:

0.122

AC:

4266

AN:

35058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4504

9009

13513

18018

22522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3548

7096

10644

14192

17740

<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:

0.140

AC:

21256

AN:

151940

Hom.:

1650

Cov.:

AF XY:

0.140

AC XY:

10414

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.167

AC:

6928

AN:

41416

American (AMR)

AF:

0.212

AC:

3239

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0946

AC:

328

AN:

3468

East Asian (EAS)

AF:

0.113

AC:

586

AN:

5168

South Asian (SAS)

AF:

0.0590

AC:

284

AN:

4816

European-Finnish (FIN)

AF:

0.108

AC:

1140

AN:

10580

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8351

AN:

67922

Other (OTH)

AF:

0.130

AC:

274

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

912

1824

2736

3648

4560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.129

Hom.:

546

Bravo

AF:

0.146

Asia WGS

AF:

0.0970

AC:

336

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

(source)

DANN

Benign

0.87

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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