dbSNP rs45474992: BBC3:c.*495G>A (chr19-47221307-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_014417.5(BBC3):c.*495G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0238 in 173,826 control chromosomes in the GnomAD database, including 79 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 0.024 ( 67 hom., cov: 30)

Exomes 𝑓: 0.024 ( 12 hom. )

Consequence

BBC3
NM_014417.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.84

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0238 (3612/152008) while in subpopulation NFE AF = 0.0343 (2327/67934). AF 95% confidence interval is 0.0331. There are 67 homozygotes in GnomAd4. There are 1737 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBC3	NM_014417.5 link	c.*495G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000439096.3	NP_055232.1	Q9BXH1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBC3	ENST00000439096.3 link	c.*495G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_014417.5	ENSP00000395862.2		Q9BXH1-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3614

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00549

Gnomad AMI

AF:

0.0872

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.0414

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0202

GnomAD4 exome

AF:

0.0244

AC:

532

AN:

21818

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

286

AN XY:

11412

show subpopulations

African (AFR)

AF:

0.00510

AC:

AN:

392

American (AMR)

AF:

0.0273

AC:

AN:

330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

694

East Asian (EAS)

AF:

0.00

AC:

AN:

450

South Asian (SAS)

AF:

0.0272

AC:

AN:

3092

European-Finnish (FIN)

AF:

0.0181

AC:

AN:

1158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0272

AC:

389

AN:

14288

Other (OTH)

AF:

0.0205

AC:

AN:

1318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

111

139

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:

0.0238

AC:

3612

AN:

152008

Hom.:

Cov.:

AF XY:

0.0234

AC XY:

1737

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00547

AC:

227

AN:

41486

American (AMR)

AF:

0.0232

AC:

354

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.000389

AC:

AN:

5136

South Asian (SAS)

AF:

0.0276

AC:

133

AN:

4816

European-Finnish (FIN)

AF:

0.0414

AC:

438

AN:

10582

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0343

AC:

2327

AN:

67934

Other (OTH)

AF:

0.0200

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

168

335

503

670

838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0298

Hom.:

Bravo

AF:

0.0224

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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