rs12957119

Variant names:

• chr18-63213922-A-C
• rs12957119
• NM_000633.3:c.586-85163T>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.586-85163T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,042 control chromosomes in the GnomAD database, including 2,569 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 0.18 (2569 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421
• Publications: 5 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]

ENSG00000308299 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-85163T>G		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-85163T>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.586-85163T>G		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27454 AN: 151924 Hom.: 2566 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.181 AC: 27464 AN: 152042 Hom.: 2569 Cov.: 31 AF XY: 0.177 AC XY: 13175 AN XY: 74304

African (AFR) AF: 0.192 AC: 7980 AN: 41460

American (AMR) AF: 0.140 AC: 2140 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3468

East Asian (EAS) AF: 0.164 AC: 850 AN: 5176

South Asian (SAS) AF: 0.109 AC: 528 AN: 4828

European-Finnish (FIN) AF: 0.175 AC: 1843 AN: 10548

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13064 AN: 67988

Other (OTH) AF: 0.200 AC: 419 AN: 2100

Alfa AF: 0.185 Hom.: 1354

Bravo AF: 0.180

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.82
PhyloP100		0.42
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: rs12957119; hg19: chr18-60881155;