18-63319604-G-T

Position:

• chr18-63319604-G-T

Variant summary

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

The ENST00000333681.5(BCL2):​c.-717C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 225,270 control chromosomes in the GnomAD database, including 25,508 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 0.44 (16590 hom., cov: 32)
  • Exomes 𝑓: 0.48 (8918 hom.)
• Consequence: BCL2 ENST00000333681.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.-717C>A		5_prime_UTR_variant	1/3	ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.-717C>A		5_prime_UTR_variant	1/3	1	NM_000633.3	ENSP00000329623	P1
BCL2	ENST00000398117.1	c.-938C>A		5_prime_UTR_variant	1/2	1		ENSP00000381185	P1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67461 AN: 151906 Hom.: 16583 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.484 AC: 35476 AN: 73246 Hom.: 8918 Cov.: 0 AF XY: 0.486 AC XY: 16449 AN XY: 33838

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.418

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.444 AC: 67495 AN: 152024 Hom.: 16590 Cov.: 32 AF XY: 0.445 AC XY: 33110 AN XY: 74326

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.482

Alfa AF: 0.468 Hom.: 3517

Bravo AF: 0.440

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
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: rs2279115; hg19: chr18-60986837;