rs12457893

chr18-63258928-A-Cchr18-63258928-A-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+59154T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,206 control chromosomes in the GnomAD database, including 12,791 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 0.40 (12791 hom., cov: 33)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966

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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.585+59154T>G		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.585+59154T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.585+59154T>G		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60478 AN: 152088 Hom.: 12788 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.397 AC: 60496 AN: 152206 Hom.: 12791 Cov.: 33 AF XY: 0.396 AC XY: 29484 AN XY: 74418

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.414

Alfa AF: 0.451 Hom.: 28946

Bravo AF: 0.390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	14
Dann	Benign	0.81

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: rs12457893; hg19: chr18-60926161;