chr18-63232095-C-T

Variant names:

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

ENSG00000308299 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.153 AC: 6340 AN: 41420

American (AMR) AF: 0.420 AC: 6410 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1940 AN: 3462

East Asian (EAS) AF: 0.184 AC: 956 AN: 5188

South Asian (SAS) AF: 0.439 AC: 2110 AN: 4802

European-Finnish (FIN) AF: 0.550 AC: 5762 AN: 10478

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.586 AC: 39749 AN: 67854

Other (OTH) AF: 0.409 AC: 860 AN: 2102

Alfa AF: 0.526 Hom.: 11863

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
PhyloP100		-1.8
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: rs7231914; hg19: chr18-60899328;