18-63136460-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):c.586-7701T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,114 control chromosomes in the GnomAD database, including 40,662 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 0.71 (40662 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.586-7701T>A		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.586-7701T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.586-7701T>A		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108547 AN: 151996 Hom.: 40663 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.714 AC: 108565 AN: 152114 Hom.: 40662 Cov.: 32 AF XY: 0.708 AC XY: 52612 AN XY: 74354

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.750

Alfa AF: 0.774 Hom.: 5795

Bravo AF: 0.702

Asia WGS AF: 0.557 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.032
Dann	Benign	0.79

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: rs8092560; hg19: chr18-60803693;