rs12968517

Variant names:

• chr18-63274738-C-T
• rs12968517
• NM_000633.3:c.585+43344G>A

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+43344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,002 control chromosomes in the GnomAD database, including 9,922 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 0.36 (9922 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 6 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 (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+43344G>A		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+43344G>A		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+43344G>A		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53988 AN: 151884 Hom.: 9916 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.355 AC: 54018 AN: 152002 Hom.: 9922 Cov.: 31 AF XY: 0.359 AC XY: 26659 AN XY: 74290

African (AFR) AF: 0.274 AC: 11338 AN: 41446

American (AMR) AF: 0.406 AC: 6205 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3466

East Asian (EAS) AF: 0.335 AC: 1733 AN: 5174

South Asian (SAS) AF: 0.411 AC: 1978 AN: 4816

European-Finnish (FIN) AF: 0.398 AC: 4202 AN: 10550

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25752 AN: 67958

Other (OTH) AF: 0.388 AC: 816 AN: 2104

Alfa AF: 0.373 Hom.: 3582

Bravo AF: 0.349

Asia WGS AF: 0.396 AC: 1376 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	0.083
DANN	Benign	0.64
PhyloP100		-1.8
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: rs12968517; hg19: chr18-60941971;