18-63153338-A-G

Variant names:

• chr18-63153338-A-G
• rs956572
• NM_000633.3:c.586-24579T>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.586-24579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,056 control chromosomes in the GnomAD database, including 31,966 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 0.64 (31966 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 30 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 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.586-24579T>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.586-24579T>C		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.586-24579T>C		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000678301.1		c.24+4735T>C		intron	N/A	ENSP00000504546.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97666 AN: 151938 Hom.: 31917 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.643 AC: 97768 AN: 152056 Hom.: 31966 Cov.: 32 AF XY: 0.641 AC XY: 47653 AN XY: 74306

African (AFR) AF: 0.761 AC: 31558 AN: 41486

American (AMR) AF: 0.594 AC: 9080 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2227 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2885 AN: 5174

South Asian (SAS) AF: 0.669 AC: 3228 AN: 4824

European-Finnish (FIN) AF: 0.592 AC: 6241 AN: 10542

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.596 AC: 40519 AN: 67960

Other (OTH) AF: 0.651 AC: 1372 AN: 2108

Alfa AF: 0.616 Hom.: 87299

Bravo AF: 0.647

Asia WGS AF: 0.600 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.77
DANN	Benign	0.36
PhyloP100		-1.4
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: rs956572; hg19: chr18-60820571;