18-63311353-G-T

Variant names:

• chr18-63311353-G-T
• rs12458289
• NM_000633.3:c.585+6729C>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+6729C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,084 control chromosomes in the GnomAD database, including 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 0.097 (866 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 12 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 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+6729C>A		intron	N/A	NP_000624.2
	BCL2	NM_001438935.1		c.585+6729C>A		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+6729C>A		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.585+6729C>A		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000677227.1		n.585+6729C>A		intron	N/A	ENSP00000504566.1

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14809 AN: 151966 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.0974 AC: 14820 AN: 152084 Hom.: 866 Cov.: 32 AF XY: 0.0993 AC XY: 7384 AN XY: 74348

African (AFR) AF: 0.0711 AC: 2948 AN: 41478

American (AMR) AF: 0.157 AC: 2393 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 219 AN: 3466

East Asian (EAS) AF: 0.272 AC: 1406 AN: 5160

South Asian (SAS) AF: 0.0637 AC: 307 AN: 4816

European-Finnish (FIN) AF: 0.0789 AC: 836 AN: 10590

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0938 AC: 6376 AN: 67974

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.0952 Hom.: 1588

Bravo AF: 0.105

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.66
PhyloP100		0.24
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: rs12458289; hg19: chr18-60978586;