rs4987843

chr18-63128308-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.*317G>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 0.132 in 262,416 control chromosomes in the GnomAD database, including 3,171 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 0.15 (2375 hom., cov: 33)
  • Exomes 𝑓: 0.10 (796 hom.)
• Consequence: BCL2 NM_000633.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.*317G>A		3_prime_UTR_variant	3/3	ENST00000333681.5
BCL2	XM_047437733.1	c.*317G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.*317G>A		3_prime_UTR_variant	3/3	1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23207 AN: 152134 Hom.: 2365 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.103 AC: 11341 AN: 110164 Hom.: 796 Cov.: 0 AF XY: 0.102 AC XY: 5399 AN XY: 53140

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.0972

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.00150

Gnomad4 SAS exome AF: 0.0518

Gnomad4 FIN exome AF: 0.0775

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.153 AC: 23235 AN: 152252 Hom.: 2375 Cov.: 33 AF XY: 0.147 AC XY: 10954 AN XY: 74464

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.0867

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.168

Alfa AF: 0.120 Hom.: 1396

Bravo AF: 0.163

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	13
Dann	Benign	0.83

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: rs4987843; hg19: chr18-60795541; COSMIC: COSV61375477;