rs45474992

Variant names:

• chr19-47221307-C-T
• rs45474992
• NM_014417.5:c.*495G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 67 AR gene

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.*495G>A		3_prime_UTR	Exon 4 of 4	NP_055232.1	Q9BXH1-1
	BBC3	NM_001127240.3		c.*394G>A		3_prime_UTR	Exon 4 of 4	NP_001120712.1	Q96PG8-2
	BBC3	NM_001127241.3		c.*495G>A		3_prime_UTR	Exon 3 of 3	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.*495G>A		3_prime_UTR	Exon 4 of 4	ENSP00000395862.2	Q9BXH1-1
	BBC3	ENST00000449228.5	TSL:1	c.*394G>A		3_prime_UTR	Exon 4 of 4	ENSP00000404503.1	Q96PG8-2
	BBC3	ENST00000341983.8	TSL:1	c.*495G>A		3_prime_UTR	Exon 3 of 3	ENSP00000341155.4	Q9BXH1-2

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

African (AFR) AF: 0.00510 AC: 2 AN: 392

American (AMR) AF: 0.0273 AC: 9 AN: 330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 694

East Asian (EAS) AF: 0.00 AC: 0 AN: 450

South Asian (SAS) AF: 0.0272 AC: 84 AN: 3092

European-Finnish (FIN) AF: 0.0181 AC: 21 AN: 1158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 96

European-Non Finnish (NFE) AF: 0.0272 AC: 389 AN: 14288

Other (OTH) AF: 0.0205 AC: 27 AN: 1318

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

African (AFR) AF: 0.00547 AC: 227 AN: 41486

American (AMR) AF: 0.0232 AC: 354 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5136

South Asian (SAS) AF: 0.0276 AC: 133 AN: 4816

European-Finnish (FIN) AF: 0.0414 AC: 438 AN: 10582

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0343 AC: 2327 AN: 67934

Other (OTH) AF: 0.0200 AC: 42 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.93
PhyloP100		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs45474992; hg19: chr19-47724564;