rs2062011

chr18-63208881-T-Achr18-63208881-T-C

Variant summary

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

The NM_000633.3(BCL2):c.586-80122A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,082 control chromosomes in the GnomAD database, including 4,517 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 0.23 (4517 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.586-80122A>T		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.586-80122A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.586-80122A>T		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35118 AN: 151964 Hom.: 4516 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.231 AC: 35122 AN: 152082 Hom.: 4517 Cov.: 31 AF XY: 0.241 AC XY: 17899 AN XY: 74336

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.219

Alfa AF: 0.146 Hom.: 260

Bravo AF: 0.217

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Benign	0.76

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: rs2062011; hg19: chr18-60876114;