rs12968517

Positions:

• chr18-63274738-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+43344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,002 control chromosomes in the GnomAD database, including 9,922 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 0.36 (9922 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+43344G>A		intron_variant		ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+43344G>A		intron_variant			XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+43344G>A		intron_variant		1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53988 AN: 151884 Hom.: 9916 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.355 AC: 54018 AN: 152002 Hom.: 9922 Cov.: 31 AF XY: 0.359 AC XY: 26659 AN XY: 74290

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.388

Alfa AF: 0.372 Hom.: 3119

Bravo AF: 0.349

Asia WGS AF: 0.396 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.083
DANN	Benign	0.64

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: rs12968517; hg19: chr18-60941971;