rs17759659

Variant names:

• chr18-63291411-A-G
• rs17759659
• NM_000633.3:c.585+26671T>C

Variant summary

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

The NM_000633.3(BCL2):​c.585+26671T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,154 control chromosomes in the GnomAD database, including 9,543 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 0.32 (9543 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 19 publications found

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+26671T>C		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+26671T>C		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.585+26671T>C		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47990 AN: 152034 Hom.: 9540 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.315 AC: 47991 AN: 152154 Hom.: 9543 Cov.: 32 AF XY: 0.316 AC XY: 23509 AN XY: 74370

African (AFR) AF: 0.0789 AC: 3277 AN: 41544

American (AMR) AF: 0.336 AC: 5131 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3470

East Asian (EAS) AF: 0.123 AC: 636 AN: 5186

South Asian (SAS) AF: 0.359 AC: 1733 AN: 4822

European-Finnish (FIN) AF: 0.476 AC: 5025 AN: 10564

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29559 AN: 67966

Other (OTH) AF: 0.336 AC: 710 AN: 2112

Alfa AF: 0.369 Hom.: 2639

Bravo AF: 0.295

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0030
DANN	Benign	0.47
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17759659; hg19: chr18-60958644;