rs4987827

Positions:

• chr18-63139665-G-T

Variant summary

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

The NM_000633.3(BCL2):​c.586-10906C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,080 control chromosomes in the GnomAD database, including 5,027 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 0.25 (5027 hom., cov: 33)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-10906C>A		intron_variant		ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-10906C>A		intron_variant			XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.586-10906C>A		intron_variant		1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37366 AN: 151962 Hom.: 5032 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.246 AC: 37353 AN: 152080 Hom.: 5027 Cov.: 33 AF XY: 0.241 AC XY: 17928 AN XY: 74346

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.248

Alfa AF: 0.273 Hom.: 950

Bravo AF: 0.237

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.45

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: rs4987827; hg19: chr18-60806898; COSMIC: COSV61388335;