rs2850760

Positions:

• chr18-63299590-T-C

Variant summary

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

The NM_000633.3(BCL2):​c.585+18492A>G 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 152,074 control chromosomes in the GnomAD database, including 15,732 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 (15732 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

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=-0.89).
• 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+18492A>G		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.585+18492A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.585+18492A>G		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63515 AN: 151956 Hom.: 15716 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.418 AC: 63553 AN: 152074 Hom.: 15732 Cov.: 31 AF XY: 0.419 AC XY: 31153 AN XY: 74342

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.446

Alfa AF: 0.500 Hom.: 4191

Bravo AF: 0.400

Asia WGS AF: 0.311 AC: 1082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.23

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: rs2850760; hg19: chr18-60966823;