NM_000633.3:c.586-14460G>A

Variant names:

• chr18-63143219-C-T
• rs4456611
• NM_000633.3:c.586-14460G>A

Variant summary

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

The NM_000633.3(BCL2):​c.586-14460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,086 control chromosomes in the GnomAD database, including 19,221 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 0.50 (19221 hom., cov: 33)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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 (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-14460G>A		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-14460G>A		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.586-14460G>A		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76181 AN: 151968 Hom.: 19204 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.501 AC: 76242 AN: 152086 Hom.: 19221 Cov.: 33 AF XY: 0.500 AC XY: 37186 AN XY: 74346

Gnomad4 AFR AF: 0.494 AC: 0.49436 AN: 0.49436

Gnomad4 AMR AF: 0.477 AC: 0.476851 AN: 0.476851

Gnomad4 ASJ AF: 0.525 AC: 0.525072 AN: 0.525072

Gnomad4 EAS AF: 0.623 AC: 0.622583 AN: 0.622583

Gnomad4 SAS AF: 0.527 AC: 0.526982 AN: 0.526982

Gnomad4 FIN AF: 0.469 AC: 0.469413 AN: 0.469413

Gnomad4 NFE AF: 0.504 AC: 0.503855 AN: 0.503855

Gnomad4 OTH AF: 0.508 AC: 0.50759 AN: 0.50759

Alfa AF: 0.506 Hom.: 75864

Bravo AF: 0.501

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.41
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

Publications

LitVar

Other links and lift over

dbSNP: rs4456611; hg19: chr18-60810452;