ENST00000449228.5:c.-357A>G

Variant names:

• chr19-47232959-T-C
• rs2032809
• ENST00000449228.5:c.-357A>G

Variant summary

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

The ENST00000449228.5(BBC3):​c.-357A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,112 control chromosomes in the GnomAD database, including 33,764 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 0.66 (33764 hom., cov: 33)
• Consequence: BBC3 ENST00000449228.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBC3	XM_006723141.4	c.-193A>G		upstream_gene_variant			XP_006723204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBC3	ENST00000449228.5	c.-357A>G		upstream_gene_variant		1		ENSP00000404503.1
BBC3	ENST00000341983.8	c.-357A>G		upstream_gene_variant		1		ENSP00000341155.4
BBC3	ENST00000300880.11	c.-357A>G		upstream_gene_variant		1		ENSP00000300880.7

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99787 AN: 151994 Hom.: 33722 Cov.: 33

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.656

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.657 AC: 99881 AN: 152112 Hom.: 33764 Cov.: 33 AF XY: 0.652 AC XY: 48511 AN XY: 74348

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.658

Alfa AF: 0.592 Hom.: 29183

Bravo AF: 0.666

Asia WGS AF: 0.639 AC: 2222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.70
DANN	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2032809; hg19: chr19-47736216;