rs1982673

chr18-63130782-A-Cchr18-63130782-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.586-2023T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,100 control chromosomes in the GnomAD database, including 2,850 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 0.18 (2850 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2	NM_000633.3	c.586-2023T>G		intron_variant		ENST00000333681.5
BCL2	XM_047437733.1	c.586-2023T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2	ENST00000333681.5	c.586-2023T>G		intron_variant		1	NM_000633.3	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27540 AN: 151982 Hom.: 2839 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.181 AC: 27580 AN: 152100 Hom.: 2850 Cov.: 32 AF XY: 0.189 AC XY: 14041 AN XY: 74360

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.160

Alfa AF: 0.158 Hom.: 2902

Bravo AF: 0.180

Asia WGS AF: 0.300 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	10
Dann	Benign	0.87

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: rs1982673; hg19: chr18-60798015;