rs4987827

Variant names:

• chr18-63139665-G-T
• rs4987827
• NM_000633.3:c.586-10906C>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.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
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	NM_000633.3	MANE Select	c.586-10906C>A		intron	N/A	NP_000624.2	P10415-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2	ENST00000333681.5	TSL:1 MANE Select	c.586-10906C>A		intron	N/A	ENSP00000329623.3	P10415-1
	BCL2	ENST00000398117.1	TSL:1	c.586-10906C>A		intron	N/A	ENSP00000381185.1	P10415-1
	BCL2	ENST00000678301.1		c.25-10906C>A		intron	N/A	ENSP00000504546.1	A0A7I2V5Q9

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

African (AFR) AF: 0.165 AC: 6859 AN: 41458

American (AMR) AF: 0.192 AC: 2935 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3470

East Asian (EAS) AF: 0.219 AC: 1133 AN: 5172

South Asian (SAS) AF: 0.191 AC: 921 AN: 4824

European-Finnish (FIN) AF: 0.265 AC: 2801 AN: 10570

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20772 AN: 67974

Other (OTH) AF: 0.248 AC: 524 AN: 2112

Alfa AF: 0.270 Hom.: 965

Bravo AF: 0.237

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.45
PhyloP100		-0.18
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: rs4987827; hg19: chr18-60806898; COSMIC: COSV61388335;