NM_000633.3:c.585+6302C>T

Variant names:

• chr18-63311780-G-A
• rs949037
• NM_000633.3:c.585+6302C>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.585+6302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,908 control chromosomes in the GnomAD database, including 14,536 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 0.44 (14536 hom., cov: 32)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43
• Publications: 19 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 (AFR) allele frequency at 95% confidence interval = 0.473 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.585+6302C>T		intron	N/A	NP_000624.2	P10415-1
	BCL2	NM_001438935.1		c.585+6302C>T		intron	N/A	NP_001425864.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.585+6302C>T		intron	N/A	ENSP00000329623.3	P10415-1
	BCL2	ENST00000398117.1	TSL:1	c.585+6302C>T		intron	N/A	ENSP00000381185.1	P10415-1
	BCL2	ENST00000677227.1		n.585+6302C>T		intron	N/A	ENSP00000504566.1	A0A7I2V5Q7

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66212 AN: 151792 Hom.: 14537 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.436 AC: 66227 AN: 151908 Hom.: 14536 Cov.: 32 AF XY: 0.433 AC XY: 32127 AN XY: 74262

African (AFR) AF: 0.479 AC: 19811 AN: 41390

American (AMR) AF: 0.382 AC: 5826 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1723 AN: 5174

South Asian (SAS) AF: 0.417 AC: 2011 AN: 4822

European-Finnish (FIN) AF: 0.424 AC: 4477 AN: 10550

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29155 AN: 67948

Other (OTH) AF: 0.419 AC: 882 AN: 2104

Alfa AF: 0.431 Hom.: 40404

Bravo AF: 0.433

Asia WGS AF: 0.377 AC: 1310 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	0.0070
DANN	Benign	0.68
PhyloP100		-2.4
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: rs949037; hg19: chr18-60979013;