rs11152377

Positions:

• chr18-63305213-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+12869A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,208 control chromosomes in the GnomAD database, including 9,304 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 0.31 (9304 hom., cov: 33)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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 = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+12869A>G		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+12869A>G		intron_variant		1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47504 AN: 152088 Hom.: 9297 Cov.: 33

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.312 AC: 47520 AN: 152208 Hom.: 9304 Cov.: 33 AF XY: 0.313 AC XY: 23267 AN XY: 74418

Gnomad4 AFR AF: 0.0801

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.334

Alfa AF: 0.406 Hom.: 17452

Bravo AF: 0.293

Asia WGS AF: 0.205 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.62

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: rs11152377; hg19: chr18-60972446;