chr19-47232959-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBC3	ENST00000449228.5	TSL:1	c.-357A>G		upstream_gene	N/A	ENSP00000404503.1
	BBC3	ENST00000341983.8	TSL:1	c.-357A>G		upstream_gene	N/A	ENSP00000341155.4
	BBC3	ENST00000300880.11	TSL:1	c.-357A>G		upstream_gene	N/A	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

African (AFR) AF: 0.830 AC: 34458 AN: 41510

American (AMR) AF: 0.603 AC: 9201 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2236 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2963 AN: 5172

South Asian (SAS) AF: 0.654 AC: 3157 AN: 4828

European-Finnish (FIN) AF: 0.531 AC: 5599 AN: 10554

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40085 AN: 67988

Other (OTH) AF: 0.658 AC: 1392 AN: 2116

Alfa AF: 0.595 Hom.: 37949

Bravo AF: 0.666

Asia WGS AF: 0.639 AC: 2222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.70
DANN	Benign	0.30
PhyloP100		-2.3
PromoterAI		-0.079	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2032809; hg19: chr19-47736216;