18-63136460-A-T

Variant names:

• chr18-63136460-A-T
• rs8092560
• NM_000633.3:c.586-7701T>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.586-7701T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,114 control chromosomes in the GnomAD database, including 40,662 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 0.71 (40662 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 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.586-7701T>A		intron	N/A	NP_000624.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.586-7701T>A		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.586-7701T>A		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000678301.1		c.25-7701T>A		intron	N/A	ENSP00000504546.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108547 AN: 151996 Hom.: 40663 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.714 AC: 108565 AN: 152114 Hom.: 40662 Cov.: 32 AF XY: 0.708 AC XY: 52612 AN XY: 74354

African (AFR) AF: 0.513 AC: 21284 AN: 41460

American (AMR) AF: 0.732 AC: 11184 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2776 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2079 AN: 5162

South Asian (SAS) AF: 0.567 AC: 2735 AN: 4822

European-Finnish (FIN) AF: 0.794 AC: 8417 AN: 10600

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57514 AN: 68002

Other (OTH) AF: 0.750 AC: 1584 AN: 2112

Alfa AF: 0.774 Hom.: 5795

Bravo AF: 0.702

Asia WGS AF: 0.557 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.032
DANN	Benign	0.79
PhyloP100		-1.4
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: rs8092560; hg19: chr18-60803693;