18-63153843-T-C

Variant names:

• chr18-63153843-T-C
• rs7230970
• NM_000633.3:c.586-25084A>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.586-25084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,046 control chromosomes in the GnomAD database, including 17,169 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 0.46 (17169 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-25084A>G		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-25084A>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.586-25084A>G		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69738 AN: 151928 Hom.: 17131 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.459 AC: 69822 AN: 152046 Hom.: 17169 Cov.: 32 AF XY: 0.451 AC XY: 33531 AN XY: 74334

African (AFR) AF: 0.619 AC: 25628 AN: 41432

American (AMR) AF: 0.351 AC: 5360 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1659 AN: 3466

East Asian (EAS) AF: 0.262 AC: 1357 AN: 5174

South Asian (SAS) AF: 0.438 AC: 2110 AN: 4818

European-Finnish (FIN) AF: 0.315 AC: 3328 AN: 10568

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28830 AN: 67980

Other (OTH) AF: 0.483 AC: 1020 AN: 2112

Alfa AF: 0.419 Hom.: 12201

Bravo AF: 0.466

Asia WGS AF: 0.387 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.82
PhyloP100		0.65
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: rs7230970; hg19: chr18-60821076;