rs8089538

chr18-63276318-A-G

Variant summary

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

The NM_000633.3(BCL2):c.585+41764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,060 control chromosomes in the GnomAD database, including 9,471 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 0.35 (9471 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831

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 (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.585+41764T>C		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.585+41764T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.585+41764T>C		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52514 AN: 151942 Hom.: 9477 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.345 AC: 52509 AN: 152060 Hom.: 9471 Cov.: 32 AF XY: 0.344 AC XY: 25556 AN XY: 74334

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.363

Alfa AF: 0.388 Hom.: 11458

Bravo AF: 0.333

Asia WGS AF: 0.293 AC: 1018 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.3
Dann	Benign	0.78

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: rs8089538; hg19: chr18-60943551;