rs45474992

Positions:

• chr19-47221307-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_014417.5(BBC3):​c.*495G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0238 in 173,826 control chromosomes in the GnomAD database, including 79 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 0.024 (67 hom., cov: 30)
  • Exomes 𝑓: 0.024 (12 hom.)
• Consequence: BBC3 NM_014417.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.84

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0238 (3612/152008) while in subpopulation NFE AF= 0.0343 (2327/67934). AF 95% confidence interval is 0.0331. There are 67 homozygotes in gnomad4. There are 1737 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBC3	NM_014417.5	c.*495G>A		3_prime_UTR_variant	4/4	ENST00000439096.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBC3	ENST00000439096.3	c.*495G>A		3_prime_UTR_variant	4/4	1	NM_014417.5	P1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3614 AN: 151892 Hom.: 67 Cov.: 30

Gnomad AFR AF: 0.00549

Gnomad AMI AF: 0.0872

Gnomad AMR AF: 0.0233

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0202

GnomAD4 exome AF: 0.0244 AC: 532 AN: 21818 Hom.: 12 Cov.: 0 AF XY: 0.0251 AC XY: 286 AN XY: 11412

Gnomad4 AFR exome AF: 0.00510

Gnomad4 AMR exome AF: 0.0273

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0272

Gnomad4 FIN exome AF: 0.0181

Gnomad4 NFE exome AF: 0.0272

Gnomad4 OTH exome AF: 0.0205

GnomAD4 genome AF: 0.0238 AC: 3612 AN: 152008 Hom.: 67 Cov.: 30 AF XY: 0.0234 AC XY: 1737 AN XY: 74300

Gnomad4 AFR AF: 0.00547

Gnomad4 AMR AF: 0.0232

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.0276

Gnomad4 FIN AF: 0.0414

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.0200

Alfa AF: 0.0298 Hom.: 20

Bravo AF: 0.0224

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.93
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: rs45474992; hg19: chr19-47724564;