rs1026825

Positions:

• chr18-63153042-A-G
• chr18-63153042-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.586-24283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,038 control chromosomes in the GnomAD database, including 15,922 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 (15922 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-24283T>C		intron_variant		ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-24283T>C		intron_variant			XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.586-24283T>C		intron_variant		1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68489 AN: 151920 Hom.: 15917 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.451 AC: 68520 AN: 152038 Hom.: 15922 Cov.: 32 AF XY: 0.453 AC XY: 33645 AN XY: 74316

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.431

Alfa AF: 0.476 Hom.: 24034

Bravo AF: 0.441

Asia WGS AF: 0.376 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.57

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: rs1026825; hg19: chr18-60820275;