rs4987792

Variant names:

• chr18-63184647-G-A
• rs4987792
• NM_000633.3:c.586-55888C>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.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
• Publications: 8 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=-0.8).
• 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 rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.586-55888C>T		intron_variant	Intron 2 of 2	ENST00000333681.5	NP_000624.2
BCL2	XM_047437733.1	c.586-55888C>T		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.586-55888C>T		intron_variant	Intron 2 of 2	1	NM_000633.3	ENSP00000329623.3

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

African (AFR) AF: 0.419 AC: 17395 AN: 41470

American (AMR) AF: 0.339 AC: 5189 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3468

East Asian (EAS) AF: 0.465 AC: 2412 AN: 5182

South Asian (SAS) AF: 0.476 AC: 2294 AN: 4820

European-Finnish (FIN) AF: 0.385 AC: 4080 AN: 10592

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19125 AN: 67984

Other (OTH) AF: 0.324 AC: 684 AN: 2114

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
PhyloP100		0.095
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: rs4987792; hg19: chr18-60851880;