rs1564483

chr18-63127421-C-T

Variant summary

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

The NM_000633.3(BCL2):c.*1204G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 235,960 control chromosomes in the GnomAD database, including 6,861 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 0.22 (4179 hom., cov: 32)
  • Exomes 𝑓: 0.25 (2682 hom.)
• Consequence: BCL2 NM_000633.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

Genes affected

BCL2 (HGNC:990): (BCL2 apoptosis regulator) This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.*1204G>A		3_prime_UTR_variant	3/3	ENST00000333681.5
BCL2	XM_047437733.1	c.*1204G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.*1204G>A		3_prime_UTR_variant	3/3	1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33524 AN: 152064 Hom.: 4181 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.249 AC: 20857 AN: 83778 Hom.: 2682 Cov.: 0 AF XY: 0.250 AC XY: 9712 AN XY: 38894

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.220 AC: 33518 AN: 152182 Hom.: 4179 Cov.: 32 AF XY: 0.220 AC XY: 16399 AN XY: 74402

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.208

Alfa AF: 0.254 Hom.: 6953

Bravo AF: 0.205

Asia WGS AF: 0.270 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.047
Dann	Benign	0.62

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: rs1564483; hg19: chr18-60794654; COSMIC: COSV61373676; COSMIC: COSV61373676;