NM_000633.3:c.586-26272C>A

Variant names:

• chr18-63155031-G-T
• rs899968
• NM_000633.3:c.586-26272C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):​c.586-26272C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,026 control chromosomes in the GnomAD database, including 33,673 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 0.66 (33673 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.586-26272C>A		intron	N/A	NP_000624.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.586-26272C>A		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.586-26272C>A		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000678301.1		c.24+3042C>A		intron	N/A	ENSP00000504546.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99827 AN: 151908 Hom.: 33623 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.657 AC: 99930 AN: 152026 Hom.: 33673 Cov.: 32 AF XY: 0.655 AC XY: 48711 AN XY: 74320

African (AFR) AF: 0.809 AC: 33546 AN: 41472

American (AMR) AF: 0.598 AC: 9124 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2374 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2796 AN: 5170

South Asian (SAS) AF: 0.668 AC: 3221 AN: 4822

European-Finnish (FIN) AF: 0.599 AC: 6326 AN: 10560

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40556 AN: 67950

Other (OTH) AF: 0.654 AC: 1376 AN: 2104

Alfa AF: 0.613 Hom.: 9694

Bravo AF: 0.663

Asia WGS AF: 0.602 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.79
PhyloP100		-0.66
Mutation Taster		=100/0	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: rs899968; hg19: chr18-60822264;