rs2850762

Positions:

• chr18-63298970-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.585+19112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,024 control chromosomes in the GnomAD database, including 15,728 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 0.42 (15728 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.10

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.585+19112G>A		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.585+19112G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.585+19112G>A		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63495 AN: 151906 Hom.: 15710 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.418 AC: 63538 AN: 152024 Hom.: 15728 Cov.: 32 AF XY: 0.419 AC XY: 31123 AN XY: 74316

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.450

Alfa AF: 0.479 Hom.: 2423

Bravo AF: 0.399

Asia WGS AF: 0.320 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0020
DANN	Benign	0.53

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: rs2850762; hg19: chr18-60966203;