rs3810294

Positions:

• chr19-47228572-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BBC3	NM_014417.5	c.-15-126G>A		intron_variant		ENST00000439096.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBC3	ENST00000439096.3	c.-15-126G>A		intron_variant		1	NM_014417.5	P1
BBC3	ENST00000300880.11	c.88+3943G>A		intron_variant		1
BBC3	ENST00000341983.8	c.89-1818G>A		intron_variant		1
BBC3	ENST00000449228.5	c.89-126G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21246 AN: 151822 Hom.: 1651 Cov.: 31

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

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.0883

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.0663

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.140 AC: 21256 AN: 151940 Hom.: 1650 Cov.: 31 AF XY: 0.140 AC XY: 10414 AN XY: 74262

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.0946

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0590

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.130

Alfa AF: 0.127 Hom.: 422

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
DANN	Benign	0.87
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

Other links and lift over

dbSNP: rs3810294; hg19: chr19-47731829;