NM_000633.3:c.585+85987G>A

Variant names:

• chr18-63232095-C-T
• rs7231914
• NM_000633.3:c.585+85987G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000633.3(BCL2):​c.585+85987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,772 control chromosomes in the GnomAD database, including 16,624 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 0.43 (16624 hom., cov: 31)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.585+85987G>A		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.585+85987G>A		intron_variant	Intron 1 of 1		XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.585+85987G>A		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64845 AN: 151654 Hom.: 16626 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.427 AC: 64846 AN: 151772 Hom.: 16624 Cov.: 31 AF XY: 0.425 AC XY: 31501 AN XY: 74160

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.409

Alfa AF: 0.532 Hom.: 10274

Bravo AF: 0.406

Asia WGS AF: 0.325 AC: 1131 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.54
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs7231914; hg19: chr18-60899328;