18-63178651-T-C

Variant names:

• chr18-63178651-T-C
• rs12454712
• NM_000633.3:c.586-49892A>G

Variant summary

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

The NM_000633.3(BCL2):​c.586-49892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,840 control chromosomes in the GnomAD database, including 9,947 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 0.35 (9947 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 101 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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-49892A>G		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-49892A>G		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.586-49892A>G		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53180 AN: 151722 Hom.: 9939 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.350 AC: 53197 AN: 151840 Hom.: 9947 Cov.: 31 AF XY: 0.359 AC XY: 26610 AN XY: 74168

African (AFR) AF: 0.226 AC: 9358 AN: 41416

American (AMR) AF: 0.340 AC: 5191 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1389 AN: 3460

East Asian (EAS) AF: 0.476 AC: 2449 AN: 5148

South Asian (SAS) AF: 0.558 AC: 2679 AN: 4800

European-Finnish (FIN) AF: 0.495 AC: 5219 AN: 10554

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25773 AN: 67906

Other (OTH) AF: 0.351 AC: 739 AN: 2106

Alfa AF: 0.371 Hom.: 36198

Bravo AF: 0.330

Asia WGS AF: 0.500 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.36
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: rs12454712; hg19: chr18-60845884;