rs1893806

Positions:

• chr18-63317731-C-A

Variant summary

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

The NM_000633.3(BCL2):​c.585+351G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,122,050 control chromosomes in the GnomAD database, including 153,116 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 0.45 (16759 hom., cov: 31)
  • Exomes 𝑓: 0.53 (136357 hom.)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+351G>T		intron_variant		ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+351G>T		intron_variant		1	NM_000633.3	ENSP00000329623	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67797 AN: 151672 Hom.: 16748 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.526 AC: 510431 AN: 970260 Hom.: 136357 Cov.: 33 AF XY: 0.526 AC XY: 238355 AN XY: 452762

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.447 AC: 67833 AN: 151790 Hom.: 16759 Cov.: 31 AF XY: 0.449 AC XY: 33296 AN XY: 74134

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.481

Alfa AF: 0.485 Hom.: 2858

Bravo AF: 0.442

Asia WGS AF: 0.388 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.49

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: rs1893806; hg19: chr18-60984964;