18-63139373-T-A

Variant names:

• chr18-63139373-T-A
• rs1531697
• NM_000633.3:c.586-10614A>T

Variant summary

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

The NM_000633.3(BCL2):​c.586-10614A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,256 control chromosomes in the GnomAD database, including 3,540 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 0.20 (3540 hom., cov: 33)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 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.586-10614A>T		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.586-10614A>T		intron	N/A	ENSP00000329623.3
	BCL2	ENST00000398117.1	TSL:1	c.586-10614A>T		intron	N/A	ENSP00000381185.1
	BCL2	ENST00000678301.1		c.25-10614A>T		intron	N/A	ENSP00000504546.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30732 AN: 152138 Hom.: 3522 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.202 AC: 30799 AN: 152256 Hom.: 3540 Cov.: 33 AF XY: 0.210 AC XY: 15622 AN XY: 74456

African (AFR) AF: 0.229 AC: 9504 AN: 41546

American (AMR) AF: 0.235 AC: 3603 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3472

East Asian (EAS) AF: 0.411 AC: 2126 AN: 5178

South Asian (SAS) AF: 0.413 AC: 1994 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2054 AN: 10606

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10264 AN: 68006

Other (OTH) AF: 0.186 AC: 393 AN: 2110

Alfa AF: 0.0874 Hom.: 124

Bravo AF: 0.204

Asia WGS AF: 0.330 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.63
PhyloP100		-0.26
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: rs1531697; hg19: chr18-60806606;