chr19-47228572-C-T

Variant names:

• chr19-47228572-C-T
• rs3810294
• NM_014417.5:c.-15-126G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014417.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBC3	NM_014417.5	MANE Select	c.-15-126G>A		intron	N/A	NP_055232.1	Q9BXH1-1
	BBC3	NM_001127240.3		c.89-126G>A		intron	N/A	NP_001120712.1	Q96PG8-2
	BBC3	NM_001127241.3		c.89-1818G>A		intron	N/A	NP_001120713.1	Q9BXH1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBC3	ENST00000439096.3	TSL:1 MANE Select	c.-15-126G>A		intron	N/A	ENSP00000395862.2	Q9BXH1-1
	BBC3	ENST00000449228.5	TSL:1	c.89-126G>A		intron	N/A	ENSP00000404503.1	Q96PG8-2
	BBC3	ENST00000341983.8	TSL:1	c.89-1818G>A		intron	N/A	ENSP00000341155.4	Q9BXH1-2

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

African (AFR) AF: 0.166 AC: 2928 AN: 17678

American (AMR) AF: 0.193 AC: 1510 AN: 7828

Ashkenazi Jewish (ASJ) AF: 0.0883 AC: 1099 AN: 12452

East Asian (EAS) AF: 0.145 AC: 3597 AN: 24782

South Asian (SAS) AF: 0.0663 AC: 917 AN: 13838

European-Finnish (FIN) AF: 0.106 AC: 2212 AN: 20904

Middle Eastern (MID) AF: 0.118 AC: 287 AN: 2430

European-Non Finnish (NFE) AF: 0.128 AC: 88897 AN: 693856

Other (OTH) AF: 0.122 AC: 4266 AN: 35058

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

African (AFR) AF: 0.167 AC: 6928 AN: 41416

American (AMR) AF: 0.212 AC: 3239 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 328 AN: 3468

East Asian (EAS) AF: 0.113 AC: 586 AN: 5168

South Asian (SAS) AF: 0.0590 AC: 284 AN: 4816

European-Finnish (FIN) AF: 0.108 AC: 1140 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8351 AN: 67922

Other (OTH) AF: 0.130 AC: 274 AN: 2104

Alfa AF: 0.129 Hom.: 546

Bravo AF: 0.146

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.87
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3810294; hg19: chr19-47731829;