rs7243091

Positions:

• chr18-63213329-G-A

Variant summary

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

The NM_000633.3(BCL2):​c.586-84570C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,928 control chromosomes in the GnomAD database, including 3,717 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 0.22 (3717 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.586-84570C>T		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.586-84570C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.586-84570C>T		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33237 AN: 151810 Hom.: 3720 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.219 AC: 33228 AN: 151928 Hom.: 3717 Cov.: 32 AF XY: 0.216 AC XY: 16046 AN XY: 74226

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.237

Alfa AF: 0.217 Hom.: 4936

Bravo AF: 0.215

Asia WGS AF: 0.145 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.6
DANN	Benign	0.59

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: rs7243091; hg19: chr18-60880562;