Variant 19-47221779-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001127240.3(BBC3):c.708C>T(p.Asp236Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00815 in 1,608,400 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 10 hom., cov: 31)

Exomes 𝑓: 0.0083 ( 63 hom. )

Consequence

BBC3
NM_001127240.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.335

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:

BBC3 (HGNC:):

BBC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 19-47221779-G-A is Benign according to our data. Variant chr19-47221779-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 770466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.335 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBC3	NM_014417.5 linkuse as main transcript	c.*23C>T		3_prime_UTR_variant	4/4	ENST00000439096.3	NP_055232.1	Q9BXH1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBC3	ENST00000439096.3 linkuse as main transcript	c.*23C>T		3_prime_UTR_variant	4/4	1	NM_014417.5	ENSP00000395862.2		Q9BXH1-1

Frequencies

GnomAD3 genomes

AF:

0.00647

AC:

984

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00572

AC:

1372

AN:

239888

Hom.:

AF XY:

0.00591

AC XY:

774

AN XY:

130964

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00897

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00299

Gnomad FIN exome

AF:

0.00614

Gnomad NFE exome

AF:

0.00881

Gnomad OTH exome

AF:

0.00634

GnomAD4 exome

AF:

0.00832

AC:

12121

AN:

1456158

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

6014

AN XY:

724660

show subpopulations

Gnomad4 AFR exome

AF:

0.00133

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00909

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00311

Gnomad4 FIN exome

AF:

0.00615

Gnomad4 NFE exome

AF:

0.00965

Gnomad4 OTH exome

AF:

0.00714

GnomAD4 genome

AF:

0.00646

AC:

983

AN:

152242

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

447

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00667

Hom.:

Bravo

AF:

0.00618

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00894

EpiControl

AF:

0.00797

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 20, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	BBC3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over