18-63313638-T-C

Variant names:

• chr18-63313638-T-C
• rs1462129
• NM_000633.3:c.585+4444A>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.585+4444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,016 control chromosomes in the GnomAD database, including 16,866 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 0.45 (16866 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 16 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.585+4444A>G		intron	N/A	NP_000624.2
	BCL2	NM_001438935.1		c.585+4444A>G		intron	N/A	NP_001425864.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.585+4444A>G		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.585+4444A>G		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000677227.1		n.585+4444A>G		intron	N/A	ENSP00000504566.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68135 AN: 151898 Hom.: 16854 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.448 AC: 68176 AN: 152016 Hom.: 16866 Cov.: 32 AF XY: 0.451 AC XY: 33509 AN XY: 74284

African (AFR) AF: 0.226 AC: 9377 AN: 41454

American (AMR) AF: 0.571 AC: 8711 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1445 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2085 AN: 5166

South Asian (SAS) AF: 0.418 AC: 2015 AN: 4816

European-Finnish (FIN) AF: 0.544 AC: 5740 AN: 10552

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37046 AN: 67974

Other (OTH) AF: 0.484 AC: 1024 AN: 2114

Alfa AF: 0.509 Hom.: 23012

Bravo AF: 0.443

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.31
DANN	Benign	0.58
PhyloP100		-0.82
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: rs1462129; hg19: chr18-60980871;