rs2850763

Variant names:

• chr18-63295477-A-G
• rs2850763
• NM_000633.3:c.585+22605T>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+22605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,970 control chromosomes in the GnomAD database, including 15,991 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 0.43 (15991 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+22605T>C		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+22605T>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+22605T>C		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64943 AN: 151852 Hom.: 15972 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.428 AC: 64990 AN: 151970 Hom.: 15991 Cov.: 31 AF XY: 0.429 AC XY: 31841 AN XY: 74252

African (AFR) AF: 0.182 AC: 7557 AN: 41456

American (AMR) AF: 0.480 AC: 7325 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1594 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5162

South Asian (SAS) AF: 0.422 AC: 2028 AN: 4806

European-Finnish (FIN) AF: 0.573 AC: 6043 AN: 10542

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37268 AN: 67944

Other (OTH) AF: 0.455 AC: 960 AN: 2112

Alfa AF: 0.491 Hom.: 8641

Bravo AF: 0.411

Asia WGS AF: 0.333 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.011
DANN	Benign	0.38
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2850763; hg19: chr18-60962710;