rs4987792

Positions:

• chr18-63184647-G-A

Variant summary

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

The NM_000633.3(BCL2):​c.586-55888C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,136 control chromosomes in the GnomAD database, including 9,512 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 0.35 (9512 hom., cov: 33)
• Consequence: BCL2 NM_000633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-55888C>T		intron_variant		ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-55888C>T		intron_variant			XP_047293689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.586-55888C>T		intron_variant		1	NM_000633.3	ENSP00000329623	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52503 AN: 152018 Hom.: 9495 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.345 AC: 52560 AN: 152136 Hom.: 9512 Cov.: 33 AF XY: 0.354 AC XY: 26365 AN XY: 74374

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.324

Alfa AF: 0.324 Hom.: 1029

Bravo AF: 0.342

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.3
DANN	Benign	0.86

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: rs4987792; hg19: chr18-60851880;