18-63192088-C-G

Variant names:

• chr18-63192088-C-G
• rs899967
• NM_000633.3:c.586-63329G>C

Variant summary

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

The NM_000633.3(BCL2):​c.586-63329G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,982 control chromosomes in the GnomAD database, including 29,155 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 0.60 (29155 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 15 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.712 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.586-63329G>C		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.586-63329G>C		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.586-63329G>C		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000677227.1		n.*107-63329G>C		intron	N/A	ENSP00000504566.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91796 AN: 151864 Hom.: 29145 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.604 AC: 91835 AN: 151982 Hom.: 29155 Cov.: 32 AF XY: 0.598 AC XY: 44413 AN XY: 74300

African (AFR) AF: 0.408 AC: 16893 AN: 41402

American (AMR) AF: 0.642 AC: 9814 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2379 AN: 3470

East Asian (EAS) AF: 0.531 AC: 2740 AN: 5156

South Asian (SAS) AF: 0.523 AC: 2521 AN: 4824

European-Finnish (FIN) AF: 0.615 AC: 6480 AN: 10540

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48763 AN: 67982

Other (OTH) AF: 0.634 AC: 1342 AN: 2116

Alfa AF: 0.646 Hom.: 4060

Bravo AF: 0.601

Asia WGS AF: 0.505 AC: 1757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.5
DANN	Benign	0.68
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs899967; hg19: chr18-60859321;