18-63181406-T-C

Variant names:

• chr18-63181406-T-C
• rs4940576
• NM_000633.3:c.586-52647A>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.586-52647A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,956 control chromosomes in the GnomAD database, including 36,494 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 0.69 (36494 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 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.586-52647A>G		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.586-52647A>G		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.586-52647A>G		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000677227.1		n.*107-52647A>G		intron	N/A	ENSP00000504566.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104613 AN: 151838 Hom.: 36459 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.689 AC: 104692 AN: 151956 Hom.: 36494 Cov.: 31 AF XY: 0.679 AC XY: 50441 AN XY: 74274

African (AFR) AF: 0.617 AC: 25534 AN: 41386

American (AMR) AF: 0.686 AC: 10492 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2479 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2734 AN: 5154

South Asian (SAS) AF: 0.590 AC: 2840 AN: 4812

European-Finnish (FIN) AF: 0.637 AC: 6723 AN: 10554

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51494 AN: 67976

Other (OTH) AF: 0.697 AC: 1469 AN: 2108

Alfa AF: 0.712 Hom.: 13237

Bravo AF: 0.692

Asia WGS AF: 0.565 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.093
DANN	Benign	0.33
PhyloP100		-2.4
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: rs4940576; hg19: chr18-60848639;