NM_000633.3:c.585+59154T>G

Variant names:

• chr18-63258928-A-C
• rs12457893
• NM_000633.3:c.585+59154T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+59154T>G		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+59154T>G		intron_variant	Intron 1 of 1		XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+59154T>G		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

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

African (AFR) AF: 0.265 AC: 11014 AN: 41528

American (AMR) AF: 0.377 AC: 5760 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1708 AN: 3470

East Asian (EAS) AF: 0.613 AC: 3179 AN: 5182

South Asian (SAS) AF: 0.549 AC: 2651 AN: 4828

European-Finnish (FIN) AF: 0.358 AC: 3799 AN: 10598

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 31017 AN: 67992

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.441 Hom.: 60494

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
PhyloP100		0.97
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12457893; hg19: chr18-60926161;