18-63314023-T-C

Variant names:

• chr18-63314023-T-C
• rs2051423
• NM_000633.3:c.585+4059A>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.585+4059A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,912 control chromosomes in the GnomAD database, including 16,864 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 0.45 (16863 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+4059A>G		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+4059A>G		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68122 AN: 151792 Hom.: 16851 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.449 AC: 68163 AN: 151910 Hom.: 16863 Cov.: 31 AF XY: 0.451 AC XY: 33515 AN XY: 74274

African (AFR) AF: 0.226 AC: 9367 AN: 41390

American (AMR) AF: 0.571 AC: 8721 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1444 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2084 AN: 5148

South Asian (SAS) AF: 0.418 AC: 2012 AN: 4816

European-Finnish (FIN) AF: 0.546 AC: 5760 AN: 10554

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.545 AC: 37021 AN: 67944

Other (OTH) AF: 0.484 AC: 1024 AN: 2114

Alfa AF: 0.513 Hom.: 9535

Bravo AF: 0.443

Asia WGS AF: 0.397 AC: 1382 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	14
DANN	Benign	0.51
PhyloP100		-0.59
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: rs2051423; hg19: chr18-60981256;